CN111164706B - Disease-associated microbiome characterization processes - Google Patents
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Abstract
Description
相关申请的交叉引用CROSS-REFERENCE TO RELATED APPLICATIONS
本申请要求2017年11月6日提交的美国临时申请序列号62/582,191、2017年8月14日提交的美国临时申请序列号62/545,039以及2018年4月16日提交的美国临时申请序列号62/658,308的权益,其全部内容通过引用各自结合到本文中。This application claims the benefit of U.S. Provisional Application Serial No. 62/582,191, filed on November 6, 2017, U.S. Provisional Application Serial No. 62/545,039, filed on August 14, 2017, and U.S. Provisional Application Serial No. 62/658,308, filed on April 16, 2018, the entire contents of each of which are incorporated herein by reference.
技术领域Technical Field
本公开一般涉及基因组学和微生物学。The present disclosure relates generally to genomics and microbiology.
背景技术Background Art
微生物组可以包括与生物体相关的共栖(commensal)、共生(symbiotic)和病原微生物的生态群落。人类微生物组的表征是一个复杂的过程。人类微生物组包括是人类细胞的10倍以上的微生物细胞,但是例如由于样品处理技术、遗传分析技术和用于处理大量数据的资源有限,人类微生物组的表征仍处于初期阶段。目前的知识已经清楚地建立了与多种健康状况的微生物组关联的作用,并已成为宿主遗传和环境因素对人类疾病发展的日益重视的媒介。怀疑微生物组在许多健康/疾病有关状态(例如,分娩准备、糖尿病、自身免疫性障碍、胃肠障碍、类风湿性障碍、神经障碍,等)中起到至少部分作用。此外,微生物组可以介导环境因素对人类、植物和/或动物健康的影响。考虑到微生物组在影响受试者健康方面深刻启示,应该追寻与微生物组表征、从表征中产生见解以及产生配置为矫正生态失调状态的治疗有关的工作。然而,用于分析人类微生物组和/或基于所获得的见解提供治疗措施的当前方法和系统留下了许多未回答的问题。The microbiome can include an ecological community of commensal, symbiotic and pathogenic microorganisms associated with an organism. The characterization of the human microbiome is a complex process. The human microbiome includes more than 10 times more microbial cells than human cells, but the characterization of the human microbiome is still in its early stages, for example, due to limited sample processing techniques, genetic analysis techniques and resources for processing large amounts of data. Current knowledge has clearly established the role of microbiome associations with a variety of health conditions, and has become a medium for the increasing attention of host genetics and environmental factors to the development of human diseases. It is suspected that the microbiome plays at least a partial role in many health/disease related states (e.g., preparation for childbirth, diabetes, autoimmune disorders, gastrointestinal disorders, rheumatoid disorders, neurological disorders, etc.). In addition, the microbiome can mediate the impact of environmental factors on human, plant and/or animal health. Considering the profound revelation of the microbiome in affecting the health of the subject, work related to the characterization of the microbiome, the generation of insights from the characterization and the generation of treatments configured to correct the dysbiosis state should be pursued. However, the current methods and systems for analyzing the human microbiome and/or providing therapeutic measures based on the insights obtained leave many unanswered questions.
这样,在微生物学领域中需要一种新的且有用的方法和/或系统,用于表征、监测、诊断和/或干预一种或多种与微生物有关的健康状况和/或相关联的关系(例如,与微生物和/或状况等相关的特定特征),例如用于个体化用途和/或全人群用途。Thus, there is a need in the field of microbiology for new and useful methods and/or systems for characterizing, monitoring, diagnosing and/or intervening in one or more microbial-related health conditions and/or associated relationships (e.g., specific characteristics associated with microorganisms and/or conditions, etc.), such as for individualized use and/or for use in the entire population.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
图1包括方法的实施方式的变型的流程图表示;FIG. 1 includes a flow chart representation of a variant of an embodiment of the method;
图2包括方法和系统的实施方式的变型的表示;FIG. 2 includes a representation of a variation of an embodiment of the method and system;
图3包括用于在方法的实施方式中生成表征模型的过程的变型;FIG3 includes a variation of a process for generating a characterization model in an embodiment of the method;
图4包括在方法的实施方式中基于益生菌疗法操作的机制的变型;FIG. 4 includes variations on the mechanisms by which probiotic therapy operates in embodiments of the methods;
图5包括在方法的实施方式中样品处理的变型;FIG5 includes variations in sample handling in embodiments of the method;
图6包括通知提供的实施例;FIG6 includes an embodiment of notification provision;
图7包括方法的实施方式的变型的示意性表示;FIG. 7 includes a schematic representation of a variant of an embodiment of the method;
图8A-8C包括利用模型执行表征过程的变型;8A-8C include variations of performing the characterization process using a model;
图9包括推广方法的实施方式的变型中的疗法;FIG. 9 includes a variation of the method of promoting the treatment of the disease;
图10包括微生物组表征模块的变型;FIG10 includes variations of a microbiome characterization module;
图11包括微生物组表征模块的变型;FIG11 includes variations of a microbiome characterization module;
图12包括微生物组表征模块的变型;FIG12 includes variations of a microbiome characterization module;
图13包括微生物组表征模块的变型;FIG13 includes variations of a microbiome characterization module;
图14包括微生物组表征模块的变型;FIG14 includes variations of a microbiome characterization module;
图15包括微生物组表征模块的变型;FIG15 includes variations of a microbiome characterization module;
图16包括微生物组表征模块的变型;FIG16 includes variations of a microbiome characterization module;
图17包括多位点分析的变型;FIG17 includes a variation of a multi-site analysis;
图18包括维恩图(Venn Diagram)的特定实施例,其具有来自用于肠道取样位点的不同统计技术(例如,单变量统计技术)的结果的比较;FIG. 18 includes a specific embodiment of a Venn Diagram having a comparison of results from different statistical techniques (e.g., univariate statistical techniques) for intestinal sampling sites;
图19包括从分析模块B的应用获得的降维(dimensionality reduction)的表示的特定实施例,各微生物组子系统被检测为由不同灰度级的颜色表示,并且相关模块由实心黑线表示;FIG. 19 includes a specific example of a representation of dimensionality reduction obtained from the application of analysis module B, with each microbiome subsystem detected as represented by a different grayscale color and the associated modules represented by solid black lines;
图20包括微生物分类标准和功能之间相互作用的表示的特定实施例,功能由正方形表示,分类标准由圆圈表示;FIG20 includes a specific embodiment of a representation of the interaction between microbial classification criteria and functions, with functions represented by squares and classification criteria represented by circles;
图21包括微生物组特征解释的变化的特定实施例,该微生物组特征与分析的各症状(condition)相关联,值对应于所解释的变化的平均值以及第32和第68百分位数,并且状况由主要显示(manifestation)位点组织在各板(panel)上。Figure 21 includes specific examples of variation explained by microbiome signatures associated with each condition analyzed, with values corresponding to the mean and 32nd and 68th percentiles of variation explained, and conditions organized on each panel by primary manifestation site.
图22包括集群分析的表示的特定实施例,该集群分析使用基于微生物组的显著相关性(significance correlations)以获得被分析的状况的数据驱动排列(data-drivenarrangement);FIG. 22 includes a particular embodiment of a representation of a cluster analysis using microbiome-based significance correlations to obtain a data-driven arrangement of the conditions being analyzed;
图23包括微生物组表征模块和相关联方面的变型;FIG. 23 includes variations of microbiome characterization modules and associated aspects;
图24包括微生物有关条件当中微生物组有关的关联(association)的热图的特定实施例;和FIG. 24 includes a specific embodiment of a heat map of microbiome-related associations among microbe-related conditions; and
图25包括显示集群内和集群间共患病(comorbidity)的个体数量的特定实施例。FIG. 25 includes specific examples showing the number of individuals with comorbidity within and between clusters.
具体实施方式DETAILED DESCRIPTION
实施方式的以下描述并非旨在限制实施方式,而是使任何本领域技术人员能够制造和使用。The following description of the embodiments is not intended to limit the embodiments, but rather to enable any person skilled in the art to make and use them.
1.概述1. Overview
如图1所示,用于表征一种或多种微生物有关状况(microorganism-relatedconditions)(例如,疾病有关状况,人类行为状况等)的方法100的实施方式可以包括:确定与受试者集合相关联的微生物数据集(例如,微生物序列数据集、诸如基于微生物序列数据集的微生物组组成多样性数据集、诸如基于微生物序列数据集的微生物组功能多样性数据集等)S110;和使用微生物组表征模块集合,基于微生物数据集(例如,基于衍生自微生物数据集的微生物组特征等)应用分析技术来针对一种或多种微生物有关状况(例如,人类行为状况,疾病有关状况,等)执行表征过程(例如,预处理、特征生成、特征处理、用于多个收集位点的多位点表征、用于多种微生物有关状况的交叉条件(cross-condition)分析、模型生成等)S130。As shown in FIG. 1 , an embodiment of a method 100 for characterizing one or more microorganism-related conditions (e.g., disease-related conditions, human behavior conditions, etc.) may include: determining a microbial dataset associated with a subject set (e.g., a microbial sequence dataset, a microbiome composition diversity dataset such as one based on a microbial sequence dataset, a microbiome functional diversity dataset such as one based on a microbial sequence dataset, etc.) S110; and using a microbiome characterization module set to apply analysis techniques based on the microbial dataset (e.g., based on microbiome features derived from the microbial dataset, etc.) to perform a characterization process (e.g., preprocessing, feature generation, feature processing, multi-site characterization for multiple collection sites, cross-condition analysis for multiple microbiome-related conditions, model generation, etc.) S130.
方法100的实施方式可以附加地或可替代地包括以下一项或多项:处理与该受试者集合的一种或多种微生物有关状况相关联的(例如,提供其有用信息的;对其描述;表示其;与其关联的等)补充数据集(例如,描述用户的一个或多个特性,如医疗状况历史(medical condition history)等)S120;确定用于确定预防、改善和/或以其他方式改变一种或多种微生物有关状况的疗法的疗法模型S140;处理与用户(例如,受试者、人类、动物、患者等)相关的一种或多种生物样品S150;使用表征过程,基于处理衍生自用户的生物样品的用户微生物数据集(例如,用户微生物序列数据集、用户微生物组组成数据集、用户微生物组功能数据集等)针对用户确定微生物有关表征(例如,人类行为表征、疾病有关表征等)S160;促进针对用户的一种或多种微生物有关状况的治疗干预(例如,基于微生物有关状况和/或疗法模型;等)S170;基于处理生物样品,监测针对用户的疗法的有效性,以评估随时间推移与针对用户的疗法相关联的微生物组组成和/或功能特征S180;和/或任何其他合适的操作。Embodiments of method 100 may additionally or alternatively include one or more of the following: processing a supplemental data set (e.g., describing one or more characteristics of a user, such as a medical condition history) associated with (e.g., providing useful information about; describing; representing; associated with, etc.) one or more microbial-related conditions of the subject set; history) etc.) S120; determining a therapy model for determining a therapy for preventing, ameliorating and/or otherwise altering one or more microbial-related conditions S140; processing one or more biological samples associated with a user (e.g., a subject, a human, an animal, a patient, etc.) S150; using a characterization process, determining a microbial-related characterization (e.g., a human behavior characterization, a disease-related characterization, etc.) for the user based on processing a user microbial dataset (e.g., a user microbial sequence dataset, a user microbiome composition dataset, a user microbiome function dataset, etc.) derived from the user's biological sample S160; facilitating therapeutic intervention for one or more microbial-related conditions of the user (e.g., based on a microbial-related condition and/or therapy model; etc.) S170; monitoring the effectiveness of a therapy for the user based on processing the biological sample to evaluate the microbiome composition and/or functional characteristics associated with the therapy for the user over time S180; and/or any other suitable operation.
方法100和/或系统200的实施方式可以起到应用一个或多个微生物组表征模块(例如,用于应用一种或多种分析技术等)来表征(例如,评估(assess)、评价(evaluate)、诊断、描述等)微生物有关状况和/或与微生物有关状况有关的用户(例如,人类行为状况、疾病有关状况等),诸如用于促进(facilitate)治疗干预(例如,疗法选择;疗法推广(promotion)和/或提供;疗法监测;疗法评价;等)。在一个实施例中,方法100可以包括:基于来自与该受试者集合相关联的生物样品的微生物核酸,确定与该受试者集合相关联的微生物序列数据集,其中该微生物核酸与该微生物有关状况相关联;使用微生物组表征模块集合,基于该微生物序列数据集应用分析技术集合(例如,至少一种统计检验,诸如单变量统计检验、降维技术、人工智能方法、本文中描述的其他方法等)来确定微生物组特征集合;基于微生物组特征集合(和/或任何其他合适的数据)生成微生物有关状况模型(例如,用于表型预测,诸如估计用户对微生物有关状况的倾向性分值(propensity score)等);以及基于微生物有关状况模型和来自用户的样品来确定针对用户的微生物有关状况的表征(例如,通过样品处理和计算处理生成用户微生物组特征值以与微生物有关状况模型一起使用等)。Embodiments of method 100 and/or system 200 may function to apply one or more microbiome characterization modules (e.g., for applying one or more analytical techniques, etc.) to characterize (e.g., assess, evaluate, diagnose, describe, etc.) microbiome-related conditions and/or users associated with microbiome-related conditions (e.g., human behavior conditions, disease-related conditions, etc.), such as for facilitating therapeutic interventions (e.g., therapy selection; therapy promotion and/or provision; therapy monitoring; therapy evaluation; etc.). In one embodiment, method 100 may include: determining a microbial sequence dataset associated with the subject set based on microbial nucleic acids from biological samples associated with the subject set, wherein the microbial nucleic acids are associated with the microbial-related condition; using a microbiome characterization module set, applying an analysis technique set (e.g., at least one statistical test, such as a univariate statistical test, a dimensionality reduction technique, an artificial intelligence method, other methods described herein, etc.) based on the microbial sequence dataset to determine a microbiome feature set; generating a microbiome-related condition model based on the microbiome feature set (and/or any other suitable data) (e.g., for phenotypic prediction, such as estimating a user's propensity score for a microbiome-related condition, etc.); and determining a characterization of a microbiome-related condition for a user based on the microbiome-related condition model and a sample from the user (e.g., generating a user microbiome feature value through sample processing and computational processing for use with the microbiome-related condition model, etc.).
附加地或可替代地,方法100和/或系统200的实施方式可以起到执行针对多种微生物有关状况(例如,多种微生物有关状况的表征等)的交叉条件分析(例如,使用一个或多个微生物组表征模块等)的作用,诸如在表征、诊断和/或治疗用户的情况下。在一个实施例中,方法100可以包括:基于来自与受试者集合相关联的生物样品的微生物核酸,确定与受试者集合相关联的微生物序列数据集,其中该微生物核酸与多种微生物有关状况相关联(例如,该微生物核酸与微生物组特征相关联等,该微生物组特征与多种微生物有关状况中的两种以上关联);使用微生物组表征模块集合,基于微生物序列数据集确定多条件微生物组特征集合,其中多条件(multi-condition)微生物组特征集合中的每个多条件微生物组特征均与多种微生物有关状况中的至少两个微生物有关状况相关联(例如,关于相关性(relevance)、关联性(correlation)、协方差在多种微生物有关状况中共享的特征等);基于多条件微生物组特征集合和来自用户的样品,针对用户确定多个微生物有关状况中的微生物有关状况(例如,子集、全部等)的多条件表征;以及基于该多条件表征,促进用于多种微生物有关状况中的微生物有关状况的治疗干预。Additionally or alternatively, embodiments of method 100 and/or system 200 can function to perform cross-condition analysis (e.g., using one or more microbiome characterization modules, etc.) for multiple microbial-related conditions (e.g., characterization of multiple microbial-related conditions, etc.), such as in the context of characterizing, diagnosing and/or treating a user. In one embodiment, method 100 may include: determining a microbial sequence dataset associated with a subject set based on microbial nucleic acids from biological samples associated with a subject set, wherein the microbial nucleic acids are associated with multiple microbial-related conditions (e.g., the microbial nucleic acids are associated with microbial group features, etc., and the microbial group features are associated with two or more of the multiple microbial-related conditions); using a microbial group characterization module set, determining a multi-conditional microbial group feature set based on the microbial sequence dataset, wherein each multi-conditional microbial group feature in the multi-conditional microbial group feature set is associated with at least two microbial-related conditions in the multiple microbial-related conditions (e.g., features shared in multiple microbial-related conditions regarding relevance, correlation, covariance, etc.); determining a multi-conditional characterization of microbial-related conditions (e.g., a subset, all, etc.) in multiple microbial-related conditions for a user based on the multi-conditional microbial group feature set and a sample from the user; and facilitating therapeutic intervention for a microbial-related condition in the multiple microbial-related conditions based on the multi-conditional characterization.
附加地或可替代地,方法100和/或系统200的实施方式可以识别与不同微生物有关状况相关联的微生物组特征,诸如用作生物标志物(例如,用于诊断过程、用于治疗过程等)。在实施例中,微生物有关表征可以与用户微生物组组成(例如,微生物组组成多样性等)、微生物组功能(例如,微生物组功能多样性等)和/或其他合适的微生物组相关方面中的至少一种或多种相关联。Additionally or alternatively, embodiments of method 100 and/or system 200 may identify microbiome signatures associated with different microbiome-related conditions, such as for use as biomarkers (e.g., for diagnostic procedures, for therapeutic procedures, etc.). In embodiments, the microbiome-related signatures may be associated with at least one or more of a user's microbiome composition (e.g., microbiome composition diversity, etc.), microbiome function (e.g., microbiome functional diversity, etc.), and/or other suitable microbiome-related aspects.
附加地或可替代地,实施方式可以起到促进针对微生物有关状况的治疗干预的作用,诸如通过相关联疗法的推广(例如,关于特定生理位点肠道,皮肤,鼻,口,生殖器,其他合适的生理位点,其他收集位点,等)。附加地或可替代地,实施方式可以起到生成模型(例如,诸如用于表型预测和/或预测分值的微生物组表征模块、诸如用于特征处理的机器学习模型等)的作用,诸如可以用于基于用户的微生物组(例如,用户微生物组特征;作为临床诊断;作为伴随诊断等)来表征和/或诊断用户的模型、和/或可用于针对受试者关于一种或多种微生物有关状况选择和/或提供疗法(例如,基于益生菌的治疗措施,基于噬菌体的治疗措施,基于小分子的治疗措施,临床措施,等)。附加地或可替代地,实施方式可以执行本文中描述的任何合适的功能。Additionally or alternatively, embodiments may function to promote therapeutic interventions for microbial-related conditions, such as through promotion of associated therapies (e.g., with respect to specific physiological sites: intestinal tract, skin, nose, mouth, genitals, other suitable physiological sites, other collection sites, etc.). Additionally or alternatively, embodiments may function to generate models (e.g., such as microbiome characterization modules for phenotypic prediction and/or prediction scores, such as machine learning models for feature processing, etc.), such as models that can be used to characterize and/or diagnose users based on their microbiome (e.g., user microbiome features; as clinical diagnosis; as companion diagnostics, etc.), and/or can be used to select and/or provide therapies for subjects regarding one or more microbial-related conditions (e.g., probiotic-based therapeutic measures, phage-based therapeutic measures, small molecule-based therapeutic measures, clinical measures, etc.). Additionally or alternatively, embodiments may perform any suitable functions described herein.
这样,可以使用一个或多个微生物组表征模块(例如,用于生成模型等)来处理来自受试者群体的数据(例如,与一种或多种微生物有关状况等相关联),以表征后续用户、诸如用于指示微生物有关的健康状态和/或改进领域,和/或促进治疗干预(例如,推广一种或多种疗法;促进用户的微生物组的组成和/或功能多样性向一种或多种期望的平衡状态集合的调整,诸如与改进的健康状态关联的状态,该改进的健康状态与一种或多种微生物有关状况相关联等)。方法100的变型还可以促进提供给用户的疗法的选择、监测(例如,功效监测等)和/或调节,诸如通过来自受试者的针对一种或多种微生物有关状况、随时间(在整个治疗方案的过程中,通过用户对微生物有关状况的经验程度;等)和/或跨收集位点收集和分析(例如,使用微生物组表征模块)的额外样品(例如,其中表征可以包括针对多种状况的交叉条件(cross-condition)表征等)。然而,方法100和/或系统200的任何合适的部分可以将来自人群、亚群、个体和/或其他合适的实体的数据用于任何合适的目的。Thus, data from a population of subjects (e.g., associated with one or more microbial-related conditions, etc.) can be processed using one or more microbiome characterization modules (e.g., for generating models, etc.) to characterize subsequent users, such as for indicating microbial-related health states and/or areas for improvement, and/or to facilitate therapeutic intervention (e.g., promoting one or more therapies; facilitating the adjustment of the composition and/or functional diversity of a user's microbiome toward one or more desired sets of equilibrium states, such as states associated with improved health states, which are associated with one or more microbial-related conditions, etc.). Variations of method 100 can also facilitate the selection, monitoring (e.g., efficacy monitoring, etc.) and/or adjustment of therapies provided to users, such as by collecting and analyzing additional samples from subjects for one or more microbial-related conditions, over time (throughout the course of a treatment regimen, by the user's experience with microbial-related conditions; etc.) and/or across collection sites (e.g., using microbiome characterization modules) (e.g., where characterization can include cross-condition characterization for multiple conditions, etc.). However, any suitable portion of method 100 and/or system 200 can use data from a population, subpopulation, individual, and/or other suitable entity for any suitable purpose.
方法100和/或系统200的实施方式可以优选生成和/或推广(例如,提供;存在;通知关于(notify regarding)等)针对一种或多种微生物有关状况的表征和/或疗法,所述一种或多种微生物有关状况可以包括以下一种或多种:疾病、症状、病因(例如,诱因等)、障碍、相关联风险(例如,倾向性分值等)、相关严重性、行为(例如,咖啡因消耗、习惯、饮食等)、和/或与微生物有关状况相关联的任何其他合适的方面。微生物有关状况可以包括一种或多种疾病有关状况,该疾病有关状况可以包括以下任何一种或多种:皮肤有关状况(例如,痤疮、皮肌炎、湿疹、酒渣鼻、皮肤干燥、牛皮癣、头皮屑、光敏性、皮肤粗糙、瘙痒、剥落(flaking)、脱屑(scaling)、脱皮(peeling)、细纹或裂纹、深色皮肤个体的皮肤灰白、发红、诸如可流血并导致感染的裂纹的深裂纹、头皮皮肤的瘙痒和脱屑、诸如刺激性油性皮肤的油性皮肤、皮肤对诸如护发产品等产品的敏感性、头皮微生物组的不平衡等);胃肠道有关状况(例如,肠易激综合征、炎症性肠病、溃疡性结肠炎、乳糜泻、克罗恩(Crohn’s)病、腹胀、痔疮、便秘、反流、血便、腹泻);过敏有关状况(例如,与小麦、麸质、乳制品、大豆、花生、贝类、树生坚果、蛋类相关的过敏和/或不耐受等);运动有关状况(例如,痛风、类风湿性关节炎、骨关节炎、反应性关节炎、多发性硬化症、帕金森氏病等);癌症有关状况(例如,淋巴瘤、白血病、胚细胞瘤、生殖细胞瘤、癌、肉瘤、乳腺癌、前列腺癌、基底细胞癌、皮肤癌、结肠癌、肺癌、与任何合适的生理区域相关的癌症等);心血管有关状况(例如,冠心病、炎性心脏病、瓣膜性心脏病、肥胖症、中风等);贫血状况(例如,地中海贫血、镰状细胞、恶性、范可尼、溶血性、再生障碍性、铁缺乏症等);神经有关状况(例如,注意缺陷多动障碍(attentiondeficit hyperactivity disorder,ADHD)、注意缺陷障碍(attention deficit disorder,ADD)、焦虑症、阿斯伯格(Asperger)综合症,自闭症,慢性疲劳综合症,抑郁症,等);自身免疫有关状况(例如,口炎性腹泻(Sprue)、艾滋病(AIDS)、舍格伦综合征(Sjogren’s)、系统性红斑狼疮等);内分泌有关状况(例如,肥胖、格雷夫斯病(Graves’disease)、桥本氏甲状腺炎(Hashimoto’s thyroiditis)、代谢病、I型糖尿病、II型糖尿病等);莱姆(Lyme)病状况;沟通有关状况;睡眠有关状况;代谢有关状况;体重有关状况;疼痛有关状况;遗传相关状况;慢性疾病和/或任何其他合适类型的疾病有关状况。在变型中,方法100和/或系统200实施方式部分可以在推广针对患有一种或多种微生物有关状况(例如,皮肤有关状况,等)的用户(例如,提供,等)的一种或多种靶向疗法中使用。附加地或可替代地,微生物有关状况可以包括一种或多种人类行为状况,该人类行为状况可以包括以下任何一种或多种:咖啡因消耗,酒精消耗,其他食物类消耗,饮食补充剂消耗,益生菌有关行为(例如,消耗、避免等),其他饮食行为,习惯行为(例如,吸烟,诸如低、中和/或极端运动状况的运动状况等),更年期,其他生物过程,社会行为,其他行为,和/或任何其他合适的人类行为状况。状况可以与任何合适的表型(例如,对于人类、动物、植物、真菌体可测量的表型,等)相关联。Embodiments of method 100 and/or system 200 may preferably generate and/or promote (e.g., provide; present; notify regarding, etc.) representations and/or therapies for one or more microbial-related conditions, which may include one or more of the following: diseases, symptoms, causes (e.g., predispositions, etc.), disorders, associated risks (e.g., propensity scores, etc.), associated severity, behaviors (e.g., caffeine consumption, habits, diet, etc.), and/or any other suitable aspect associated with a microbial-related condition. Microbiome-related conditions may include one or more disease-related conditions, which may include any one or more of the following: skin-related conditions (e.g., acne, dermatomyositis, eczema, rosacea, dry skin, psoriasis, dandruff, photosensitivity, rough skin, itching, flaking, scaling, peeling, fine lines or cracks, graying of the skin in dark-skinned individuals, redness, deep cracks such as fissures that can bleed and lead to infection, itching and scaling of the scalp skin, oily skin such as irritating oily skin, sensitivity of the skin to products such as hair care products, imbalance of the scalp microbiome, etc.); gastrointestinal tract-related conditions (e.g., irritable bowel syndrome, inflammatory bowel disease, ulcerative colitis, celiac disease, Crohn's disease, bloating, hemorrhoids, constipation, reflux, bloody stools, diarrhea); Allergy-related conditions (e.g., allergies and/or intolerances related to wheat, gluten, dairy, soy, peanuts, shellfish, tree nuts, eggs, etc.); sports-related conditions (e.g., gout, rheumatoid arthritis, osteoarthritis, reactive arthritis, multiple sclerosis, Parkinson's disease, etc.); cancer-related conditions (e.g., lymphoma, leukemia, blastoma, germ cell tumor, carcinoma, sarcoma, breast cancer, prostate cancer, basal cell carcinoma, skin cancer, colon cancer, lung cancer, cancer associated with any appropriate physiological area, etc.); cardiovascular-related conditions (e.g., coronary heart disease, inflammatory heart disease, valvular heart disease, obesity, stroke, etc.); anemia conditions (e.g., thalassemia, sickle cell, malignant, Fanconi, hemolytic, aplastic, iron deficiency, etc.); neurological-related conditions (e.g., attention deficit hyperactivity disorder, ... hyperactivity disorder (ADHD), attention deficit disorder (ADD), anxiety, Asperger's syndrome, autism, chronic fatigue syndrome, depression, etc.); autoimmune-related conditions (e.g., Sprue, AIDS, Sjogren's, systemic lupus erythematosus, etc.); endocrine-related conditions (e.g., obesity, Graves' disease, Hashimoto's thyroiditis, metabolic diseases, type I diabetes, type II diabetes, etc.); Lyme disease conditions; communication-related conditions; sleep-related conditions; metabolic-related conditions; weight-related conditions; pain-related conditions; genetic-related conditions; chronic diseases and/or any other suitable type of disease-related conditions. In variations, method 100 and/or system 200 embodiments may be used in promoting (e.g., providing, etc.) one or more targeted therapies to users suffering from one or more microbial-related conditions (e.g., skin-related conditions, etc.). Additionally or alternatively, microbe-related conditions may include one or more human behavior conditions, which may include any one or more of the following: caffeine consumption, alcohol consumption, other food consumption, dietary supplement consumption, probiotic-related behavior (e.g., consumption, avoidance, etc.), other dietary behaviors, habitual behaviors (e.g., smoking, exercise conditions such as low, moderate and/or extreme exercise conditions, etc.), menopause, other biological processes, social behavior, other behaviors, and/or any other suitable human behavior conditions. Conditions may be associated with any suitable phenotype (e.g., a phenotype measurable for a human, animal, plant, fungal organism, etc.).
方法100和/或系统200的实施方式可以针对单个用户实施,诸如关于应用一个或多个微生物组表征模块用于处理(例如,跨一个或多个收集位点收集的)来自用户的一个或多个生物样品,用于微生物有关表征,促进治疗干预和/或用于任何其他合适的目的(例如,用于一种或多种微生物有关状况,等)。附加地或可替代地,实施方式可以针对受试者群体(例如,包括用户,不包括用户)实施,其中受试者群体可以包括与任何合适类型特性的其他受试者相似和/或不相似的受试者(例如,关于微生物有关状况、人口统计学特征行为、微生物组组成和/或功能,等);针对用户亚组实施(例如,共享特性,例如影响微生物有关特性和/或疗法确定的特性等);针对植物、动物、微生物和/或任何其他合适的实体实施。因此,从受试者集合(例如,受试者群体、受试者集合、用户亚组等)衍生的信息可以用于为后续用户提供额外的见解。在变型中,生物样品汇总集合(aggregate set)优选与各种用户相关联并针对各种用户进行处理,诸如包括以下一种或多种的用户:不同的人口统计学(例如,性别、年龄、婚姻状态、种族、国籍、社会经济状态、性取向等),不同的微生物有关状况(例如,健康和疾病状态、不同的遗传倾向(genetic dispositions);等),不同的生活情况(例如,单独生活、与宠物生活、与其他重要的事物生活、与儿童生活等),不同的饮食习惯(例如,杂食,素食(vegetarian),严格素食者(vegan),糖消耗,酸消耗,咖啡因消耗,等),不同的行为倾向性(behavioral tendencies)(例如,身体活动水平,药物使用,饮酒,等),不同移动性水平(例如,有关在给定时间段内经过的距离),和/或任何其他合适的特性(例如,影响微生物组组成和/或功能、与之关联、和/或以其他方式与之相关联的特性等)。在实施例中,随着用户数量的增加,在方法100的部分中实施的过程预测能力可以增加,诸如关于基于用户的微生物组表征各种用户(例如,关于针对用户的样品的不同收集位点等)。然而,针对任何合适的一个或多个实体,方法100和/或系统200的部分可以以任何合适的方式执行和/或配置。Embodiments of method 100 and/or system 200 may be implemented for a single user, such as with respect to applying one or more microbiome characterization modules for processing one or more biological samples from a user (e.g., collected across one or more collection sites) for microbiome-related characterization, facilitating therapeutic intervention, and/or for any other suitable purpose (e.g., for one or more microbiome-related conditions, etc.). Additionally or alternatively, embodiments may be implemented for a subject population (e.g., including the user, excluding the user), wherein the subject population may include subjects that are similar and/or dissimilar to other subjects of any suitable type of characteristics (e.g., with respect to microbiome-related conditions, demographic characteristics, behavior, microbiome composition and/or function, etc.); for a subgroup of users (e.g., shared characteristics, such as characteristics that affect microbiome-related characteristics and/or therapy determination, etc.); for plants, animals, microorganisms, and/or any other suitable entity. Thus, information derived from a subject collection (e.g., a subject population, a subject collection, a subgroup of users, etc.) may be used to provide additional insights to subsequent users. In variations, aggregate sets of biological samples are preferably associated with and processed for various users, such as users including one or more of: different demographics (e.g., gender, age, marital status, race, nationality, socioeconomic status, sexual orientation, etc.), different microbiome-related conditions (e.g., health and disease states, different genetic dispositions; etc.), different living situations (e.g., living alone, living with pets, living with significant others, living with children, etc.), different dietary habits (e.g., omnivorous, vegetarian, vegan, sugar consumption, acid consumption, caffeine consumption, etc.), different behavioral tendencies (e.g., physical activity level, medication use, alcohol consumption, etc.), different mobility levels (e.g., regarding distance traveled in a given time period), and/or any other suitable characteristics (e.g., characteristics that affect, are associated with, and/or are otherwise associated with microbiome composition and/or function, etc.). In an embodiment, as the number of users increases, the process prediction capabilities implemented in portions of method 100 may increase, such as with respect to characterizing various users based on their microbiome (e.g., with respect to different collection sites for users' samples, etc.). However, portions of method 100 and/or system 200 may be performed and/or configured in any suitable manner for any suitable entity or entities.
本文中描述的数据(例如,微生物组表征模块输入、微生物组表征模块输出、微生物数据集、微生物组特征、微生物有关表征、疗法有关数据、用户数据、补充数据、通知等)可以与任何合适的时间指示符(temporal indicators)(例如,秒、分钟、小时、天、周等)相关联,该时间指示符包括以下一种或多种:指示数据何时被收集(例如,指示样品何时被收集的时间指示符;等)、确定、传输、接收和/或以其他方式处理的时间指示符;向由数据描述的内容提供上下文的时间指示符;(例如,与微生物有关特征相关联的时间指示符,诸如其中微生物有关表征描述了特定时间时微生物有关状况和/或用户微生物组状态等);时间指示符的变化(例如,微生物有关表征随时间的变化,诸如响应于接收疗法;样品收集、样品分析、向用户提供微生物有关表征或疗法、和/或方法100的其他合适的部分之间的等待时间(latency)等);和/或任何其他合适的与时间有关的指示符。The data described herein (e.g., microbiome characterization module inputs, microbiome characterization module outputs, microbiome datasets, microbiome features, microbiome-related features, therapy-related data, user data, supplemental data, notifications, etc.) can be associated with any suitable temporal indicators (e.g., seconds, minutes, hours, days, weeks, etc.), including one or more of the following: temporal indicators indicating when the data was collected (e.g., temporal indicators indicating when a sample was collected; etc.), determined, transmitted, received, and/or otherwise processed; temporal indicators that provide context to the content described by the data; (e.g., temporal indicators associated with microbiome-related features, such as where the microbiome-related features describe a microbiome-related condition and/or a user's microbiome status at a particular time, etc.); changes in temporal indicators (e.g., changes in microbiome-related features over time, such as in response to receiving a therapy; latency between sample collection, sample analysis, providing a microbiome-related feature or therapy to a user, and/or other suitable parts of method 100, etc.); and/or any other suitable time-related indicators.
附加地或可替代地,参数、指标(metric)、输入、输出和/或其他合适的数据可以与值类型相关联,该值类型包括:分值(例如,微生物有关状况倾向性(propensity)分值;特征相关性分值;关联性分值、协方差分值、微生物组多样性分值、严重性分值等),个体值(例如,针对不同收集位点的个体微生物有关分值,诸如状况倾向性分值,等),汇总值(例如,针对不同收集位点、基于个体微生物有关分值的总体分值等),二进制值(例如,微生物组特征存在或不存在;微生物有关状况存在或不存在等),相对值(例如,相对分类组丰度、相对微生物组功能丰度、相对特征丰度等),分类(例如,针对用户的微生物有关状况分类和/或诊断、针对状况的微生物有关状况集群分类;特征分类;行为分类;人口统计学分类等),置信水平(例如,与微生物序列数据集相关联;与微生物组多样性分值相关联;与其他微生物有关表征相关联;与其他输出相关联等),标识符(例如,识别在处理数据中使用的微生物组表征模块,等),频谱上的值和/或其他任何合适类型的值。本文中描述的任何合适类型的数据都可以用作输入(例如,用于本文中描述的不同模块、模型和/或其他合适的组件)、生成为(例如,不同模型、模块的输出等的)输出、和/或对于与方法100和/或系统200相关联的任何合适的组件,以任何合适的方式操作。Additionally or alternatively, parameters, metrics, inputs, outputs, and/or other suitable data can be associated with value types, including: scores (e.g., microbial-related condition propensity scores; feature correlation scores; association scores, covariance scores, microbiome diversity scores, severity scores, etc.), individual values (e.g., individual microbial-related scores for different collection sites, such as condition propensity scores, etc.), summary values (e.g., overall scores based on individual microbial-related scores for different collection sites, etc.), binary values (e.g., microbiome feature presence or absence; microbial The present invention also provides a method for determining the presence or absence of a microbial-related condition, such as the presence or absence of a microbial-related condition, etc.), a relative value (e.g., relative taxonomic group abundance, relative microbiome functional abundance, relative feature abundance, etc.), a classification (e.g., classification and/or diagnosis of a microbial-related condition for a user, classification of a microbial-related condition cluster for a condition; feature classification; behavior classification; demographic classification, etc.), a confidence level (e.g., associated with a microbial sequence data set; associated with a microbiome diversity score; associated with other microbial-related characterizations; associated with other outputs, etc.), an identifier (e.g., identifying a microbiome characterization module used in processing data, etc.), a value on a spectrum, and/or any other suitable type of value. Any suitable type of data described herein can be used as input (e.g., for different modules, models, and/or other suitable components described herein), generated as output (e.g., output of different models, modules, etc.), and/or operated in any suitable manner for any suitable component associated with method 100 and/or system 200.
本文中描述的方法100和/或过程的一个或多个实例和/或部分可以异步地(例如,顺序地)、同时地(例如,用微生物组表征模块的并行数据处理;同时的交叉条件分析;多重样品处理,诸如对应于与微生物有关状况相关联的靶序列的微生物核酸片段的多重扩增;执行样品处理和分析以用于基本同时地评价一组(a panel of)微生物有关状况;计算上确定微生物数据集、微生物组特征、和/或对于多个用户表征并行的微生物有关状况;诸如同时在不同线程上以并行计算以提高系统处理能力等)、与触发事件(例如,方法100的部分的执行)时间上相关(例如,基本同时,响应于,连续地,先于,随后,等)、和/或通过和/或使用本文描述的系统200、组件和/或实体的一个或多个实例以任何其他合适的顺序、以任何合适的时间和频率来执行。在一实施例中,方法100可以包括:基于使用样品处理系统的下一代测序平台(和/或其他合适的测序系统)的桥扩增底物(bridge amplificationsubstrate)处理一个或多个生物样品的微生物核酸来生成微生物数据集,以及在可操作以与下一代测序平台通信的计算设备中确定微生物组特征和微生物组功能多样性特征。然而,方法100和/或系统200可以任何合适的方式配置。One or more instances and/or portions of the method 100 and/or processes described herein can be performed asynchronously (e.g., sequentially), simultaneously (e.g., parallel data processing with a microbiome characterization module; simultaneous cross-condition analysis; multiple sample processing, such as multiple amplification of microbial nucleic acid fragments corresponding to target sequences associated with microbial-related conditions; performing sample processing and analysis for substantially simultaneous evaluation of a panel of microbial-related conditions; computationally determining microbial datasets, microbiome signatures, and/or characterizing microbial-related conditions in parallel for multiple users; such as simultaneously on different threads to parallelize computations to increase system processing capabilities, etc.), in time relation to a triggering event (e.g., execution of a portion of the method 100) (e.g., substantially simultaneously, in response to, continuously, prior to, subsequent to, etc.), and/or in any other suitable order, at any suitable time and frequency, by and/or using one or more instances of the system 200, components, and/or entities described herein. In one embodiment, method 100 may include: generating a microbial data set based on processing microbial nucleic acids of one or more biological samples using a bridge amplification substrate of a next generation sequencing platform (and/or other suitable sequencing system) of a sample processing system, and determining microbiome features and microbiome functional diversity features in a computing device operable to communicate with the next generation sequencing platform. However, method 100 and/or system 200 may be configured in any suitable manner.
2.益处2. Benefits
微生物组分析可以使针对由微生物引起的和/或以其他方式与微生物相关联的微生物有关状况的准确和/或有效表征、和/或疗法提供(例如,根据方法100的部分等)成为可能。该技术的特定实施例可以克服传统方法在表征用户状况(例如,微生物有关状况)和/或促进治疗干预中所面临的若干挑战。第一,传统方法可能需要患者访问一个或多个护理提供者,以接收针对微生物有关状况的表征和/或疗法建议(例如,通过诸如血液测试的诊断性医疗程序;等),这可能相当于(amount to)与诊断和/或治疗之前经过的时间量、医疗护理质量的不一致和/或护理提供者访问的其他方面相关联的效率低下和/或健康风险。第二,用于人类基因组测序的传统基因测序和分析技术当应用于微生物组时可能不兼容和/或效率低下(例如,其中人类微生物组可包括是人类细胞10倍以上的微生物细胞;其中可行的分析技术和利用分析技术的手段可能不同;其中最佳样品处理技术可能不同,诸如用于减少扩增偏差;其中可能采用对微生物有关表征的不同方法;其中状况和关联性的类型可能不同;其中相关联状况的起因和/或针对相关联状况的可行疗法可能不同;其中序列参考数据库可能不同;其中微生物组可能在跨越用户的不同身体区域、例如在不同的收集位点上变化;等)。第三,测序技术(例如,下一代测序、相关联技术等)的兴起已经引起了技术问题(例如,针对大量生成的序列数据的数据处理和分析的问题;以多重方式处理多种生物样品的问题;信息显示问题;疗法预测问题;疗法提供问题,等),但由于与测序遗传物质相关联的速度和数据生成方面的空前发展,这些技术问题将不存在。方法100和/或系统200的特定实施例可以为至少上述挑战赋予以技术为根基的(technologically-rooted)解决方案。Microbiome analysis can enable accurate and/or effective characterization, and/or provision of therapy for microbe-related conditions caused by and/or otherwise associated with microbes (e.g., according to portions of method 100, etc.). Certain embodiments of the technology can overcome several challenges faced by traditional methods in characterizing user conditions (e.g., microbe-related conditions) and/or facilitating therapeutic interventions. First, traditional methods may require patients to visit one or more care providers to receive characterization and/or therapy recommendations for microbe-related conditions (e.g., through diagnostic medical procedures such as blood tests; etc.), which may amount to inefficiencies and/or health risks associated with the amount of time that elapses before diagnosis and/or treatment, inconsistencies in the quality of medical care, and/or other aspects of care provider visits. Second, conventional gene sequencing and analysis techniques used for human genome sequencing may be incompatible and/or inefficient when applied to microbiomes (e.g., where the human microbiome may include more than 10 times the number of microbial cells as human cells; where feasible analysis techniques and means of utilizing analysis techniques may be different; where optimal sample processing techniques may be different, such as for reducing amplification bias; where different approaches to characterizing microorganisms may be employed; where the types of conditions and associations may be different; where the causes of associated conditions and/or feasible therapies for associated conditions may be different; where sequence reference databases may be different; where the microbiomes may vary across different body regions of the user, such as at different collection sites; etc.). Third, the rise of sequencing technologies (e.g., next generation sequencing, associated technologies, etc.) has raised technical issues (e.g., issues with data processing and analysis of large amounts of generated sequence data; issues with processing multiple biological samples in a multiplexed manner; information display issues; therapy prediction issues; therapy delivery issues, etc.), but these technical issues will not exist due to the unprecedented developments in speed and data generation associated with sequencing genetic material. Certain embodiments of the method 100 and/or system 200 may provide technologically-rooted solutions to at least the challenges discussed above.
第一,该技术的特定实施例可以将实体(例如,用户、生物样品、包括医疗设备的疗法促进系统等)转变为不同的状态或事物。例如,该技术可以将生物样品转变为能够测序和分析的成分,以生成微生物数据集和/或微生物组特征,该微生物数据集和/或微生物组特征可用于表征关于一种或多种微生物有关状况的用户(例如,诸如通过使用微生物组表征模块、下一代测序系统、多重扩增操作等)。在另一实施例中,该技术可以识别、推广(例如,提出、建议)、劝阻(discouraging)和/或提供疗法(例如,基于微生物组表征的个体化疗法等)和/或以其他方式促进治疗干预(例如,促进用户的微生物组组成、微生物组功能的改变等),这可以预防和/或改善一种或多种微生物有关状况,从而转变患者的微生物组和/或健康(例如,改进与微生物有关状况相关的健康状态;等)。在另一实施例中,该技术可以在用户的一个或多个不同生理位点(例如,一个或多个不同收集位点等)转变微生物组组成和/或功能,例如靶向和/或转变与肠道、鼻、皮肤、口和/或生殖器微生物组相关联的微生物。在另一实施例中,该技术可以控制治疗有关系统(例如,饮食系统;自动药物分配器;行为改变系统;诊断系统;疾病疗法促进系统等),以推广疗法(例如,通过针对疗法促进系统生成以执行的控制指令等),从而转变疗法促进系统。First, a specific embodiment of the technology can transform an entity (e.g., a user, a biological sample, a therapy-facilitating system including a medical device, etc.) into a different state or thing. For example, the technology can transform a biological sample into a component that can be sequenced and analyzed to generate a microbial data set and/or a microbiome signature that can be used to characterize a user with respect to one or more microbial-related conditions (e.g., such as by using a microbiome characterization module, a next-generation sequencing system, a multiplex amplification operation, etc.). In another embodiment, the technology can identify, promote (e.g., propose, suggest), discourage (discouraging) and/or provide therapy (e.g., personalized therapy based on microbiome characterization, etc.) and/or otherwise promote therapeutic intervention (e.g., promote changes in the user's microbiome composition, microbiome function, etc.), which can prevent and/or improve one or more microbial-related conditions, thereby transforming the patient's microbiome and/or health (e.g., improving health status associated with microbial-related conditions; etc.). In another embodiment, the technology can transform the microbiome composition and/or function at one or more different physiological sites of the user (e.g., one or more different collection sites, etc.), such as targeting and/or transforming microorganisms associated with the intestinal, nasal, skin, oral and/or genital microbiomes. In another embodiment, the technology can control a therapy-related system (e.g., a dietary system; an automatic medication dispenser; a behavior change system; a diagnostic system; a disease therapy promotion system, etc.) to promote a therapy (e.g., by generating control instructions for execution for a therapy promotion system, etc.), thereby transforming the therapy promotion system.
第二,该技术的特定实施例可以诸如通过促进计算机执行非预先可执行的功能,来赋予计算机有关技术中的改进(例如,改进针对微生物有关状况在存储、检索和/或处理微生物有关数据方面的计算效率;与生物样品处理相关的计算处理等)。例如,该技术可以利用微生物组表征模块集合来以非通用方式将多种分析技术应用于非通用的微生物数据集和/或微生物组特征(例如,由于样品处理技术和/或测序技术方面的进步,该微生物数据集和/或微生物组特征是最近能够生成的和/或可行的,等),用以改进微生物有关表征和/或促进针对微生物有关状况的治疗干预。Second, specific embodiments of the technology can confer improvements in computer-related technologies (e.g., improving computational efficiency in storing, retrieving, and/or processing microbial-related data for microbial-related conditions; computational processing associated with biological sample processing, etc.), such as by facilitating computers to perform non-previously executable functions. For example, the technology can utilize a collection of microbiome characterization modules to apply a variety of analytical techniques to non-universal microbial datasets and/or microbiome features in a non-universal manner (e.g., the microbial datasets and/or microbiome features are recently generated and/or feasible due to advances in sample processing technology and/or sequencing technology, etc.), to improve microbial-related characterizations and/or facilitate therapeutic interventions for microbial-related conditions.
第三,该技术的特定实施例可以在处理速度、微生物有关表征、准确性、微生物组有关疗法确定和推广、和/或关于微生物有关状况的其他合适方面方面赋予改进。例如,该技术可以利用具有非通用的微生物数据集的微生物组表征模块集合来确定、选择和/或以其他方式处理与一种或多种微生物有关状况特别相关的微生物组特征(例如,处理过的与微生物有关状况的相关性分值相关联的微生物组特征;与多种微生物有关状况相关的交叉条件微生物组特征等),这可以促进准确性(例如,通过使用最相关的微生物组特征;通过利用定制的分析技术等)、处理速度(例如,通过选择相关微生物组特征的子集;通过执行降维技术;通过利用定制的分析技术等)的改进,和/或关于表型预测(例如,微生物有关状况的指示等)、其他合适的表征、治疗干预促进和/或其他合适的目的的其他计算改进。在特定实施例中,该技术可以将特征选择规则(例如,用于组成、功能的微生物组特征选择规则;用于从补充数据集中提取的补充特征的微生物组特征选择规则等)与一种或多种微生物组表征模块一起应用,以从巨大的潜在的特征池(pool of features)(例如,从大量(a plethoraof)诸如序列数据的微生物组数据中可提取的;通过诸如单变量统计检验的统计检验可识别的;等)中选择优化的特征子集(例如,与一种或多种微生物有关状况相关的微生物组功能特征;微生物组组成多样性特征,诸如表示与微生物有关状况相关联的分类组的健康、存在、不存在和/或其他合适范围的参考相对丰度特征;可与与微生物有关状况和/或疗法响应关联的参考相对丰度特征比较的用户相对丰度特征;等),用于生成、应用、和/或以其他方式促进表征和/或疗法(例如,通过模型,等)。微生物组(例如,人类微生物组、动物微生物组等)的潜在规模可以转化为大量数据,给出了如何处理和分析大批数据以生成关于微生物有关状况的可操作的微生物组见解的问题。然而,特征选择规则和/或其他合适的计算机可实现规则可以使以下一项或多项成为可能:较短的生成和执行时间(例如,用于生成和/或应用模型;用于确定微生物有关表征和/或相关联疗法;等);优化的样品处理技术(例如,诸如在优化以改进特异性、减少扩增偏差和/或其他合适的参数的情况下,通过使用通过分类组、序列和/或与微生物有关状况相关的其他合适的数据识别引物类型、其他生物分子和/或其他样品处理成分,改进微生物核酸从生物样品的转变;等);促进结果的有效解释(interpretation)的模型简化;过度拟合的减少;与微生物有关状况有关的、随时间推移的与针对多个用户生成、存储和应用微生物组表征相关联的网络效应(例如,通过收集和处理增加数量的微生物组有关数据以改进微生物有关表征和/或疗法确定的预测能力等,该增加数量的微生物组有关数据与增加数量的用户相关联);数据存储和检索的改进(例如,存储和/或检索微生物组表征模块;存储诸如与具有不同微生物有关状况的不同用户和/或用户集合相关联的特定模型;存储与用户帐户相关联的微生物数据集;存储与一种或多种疗法和/或接受该疗法的用户相关联的疗法监测数据;存储与用户、用户集合和/或其他实体相关联的特征、微生物有关表征和/或其他合适的数据,以针对微生物有关状况改进个性化表征和/或疗法的递送,等);和/或对技术领域的其他合适的改进。Third, specific embodiments of the technology can confer improvements in processing speed, microbe-related characterization, accuracy, microbiome-related therapy determination and promotion, and/or other suitable aspects of microbe-related conditions. For example, the technology can utilize a set of microbiome characterization modules with a non-universal microbial data set to determine, select and/or otherwise process microbiome features that are particularly relevant to one or more microbe-related conditions (e.g., processed microbiome features associated with correlation scores for microbe-related conditions; cross-conditional microbiome features associated with multiple microbe-related conditions, etc.), which can promote accuracy (e.g., by using the most relevant microbiome features; by utilizing customized analysis techniques, etc.), processing speed (e.g., by selecting a subset of relevant microbiome features; by performing dimensionality reduction techniques; by utilizing customized analysis techniques, etc.), and/or other computational improvements with respect to phenotypic prediction (e.g., indication of microbe-related conditions, etc.), other suitable characterizations, promotion of therapeutic interventions, and/or other suitable purposes. In certain embodiments, the technology can apply feature selection rules (e.g., microbiome feature selection rules for composition, function; microbiome feature selection rules for supplementary features extracted from supplementary data sets, etc.) together with one or more microbiome characterization modules to select an optimized subset of features (e.g., microbiome functional features associated with one or more microbial-associated conditions; microbiome composition diversity features, such as reference relative abundance features representing healthy, present, absent, and/or other suitable ranges of taxonomic groups associated with microbial-associated conditions; user relative abundance features that can be compared to reference relative abundance features associated with microbial-associated conditions and/or therapy responses; etc.) from a large potential pool of features (e.g., extractable from a plethora of microbiome data such as sequence data; identifiable by statistical tests such as univariate statistical tests; etc.) for generating, applying, and/or otherwise facilitating characterization and/or therapy (e.g., through models, etc.). The potential size of microbiomes (e.g., human microbiomes, animal microbiomes, etc.) can translate into large amounts of data, giving rise to the problem of how to process and analyze large amounts of data to generate actionable microbiome insights about microbial-associated conditions. However, feature selection rules and/or other suitable computer-implementable rules can enable one or more of the following: shorter generation and execution time (e.g., for generating and/or applying models; for determining microorganism-related characteristics and/or associated therapies; etc.); optimized sample processing techniques (e.g., such as in the case of optimizing to improve specificity, reduce amplification bias and/or other suitable parameters, by using primer types, other biomolecules and/or other sample processing components identified by taxonomic groups, sequences and/or other suitable data related to microorganism-related conditions, improving the conversion of microbial nucleic acids from biological samples; etc.); model simplification that facilitates efficient interpretation of results; reduction of overfitting; generation, storage and application of microbiome tables related to microorganism-related conditions over time for multiple users; and/or other suitable improvements in the art.
第四,该技术的特定实施例可以相当于包括样品处理系统、微生物有关表征系统(例如,包括微生物组表征模块集合,其中各模块可具有不同但互补的功能,等)和多个用户的整个网络上的发明性功能分布,其中样品处理系统可处理来自多个用户的生物样品的基本同时的处理(例如,以多重方式),其可被微生物有关表征系统利用来生成针对微生物有关状况的个性化表征和/或治疗(例如,针对用户的微生物组进行定制,该用户的微生物组诸如与用户的饮食行为、益生菌相关行为、病史、人口统计学、其他行为、偏好等有关)。Fourth, certain embodiments of the technology can amount to an inventive distribution of functionality across a network including a sample processing system, a microbe-related characterization system (e.g., including a collection of microbiome characterization modules, each of which can have different but complementary functions, etc.), and multiple users, wherein the sample processing system can handle substantially simultaneous processing of biological samples from multiple users (e.g., in a multiplexed manner), which can be utilized by the microbe-related characterization system to generate personalized characterizations and/or treatments for microbe-related conditions (e.g., customized to a user's microbiome, such as related to the user's dietary behavior, probiotic-related behavior, medical history, demographics, other behaviors, preferences, etc.).
第五,该技术的特定实施例可以改进至少基因组学(genomics)、微生物学、微生物组有关计算、诊断、疗法、微生物组有关数字医学、一般数字医学、建模和/或其他相关领域的技术领域。在一实施例中,该技术可以利用微生物组表征模块集合来建模和/或表征不同的微生物有关状况,例如通过针对微生物有关状况进行的相关微生物特征的计算识别(例如,其可充当要在诊断中使用的生物标志物,促进治疗干预,等)。在另一实施例中,该技术可以执行交叉条件分析,以识别和评价交叉条件微生物组特征,该交叉条件微生物组特征与多种微生物有关状况(例如,疾病、表型等)相关(例如,跨多种微生物有关状况共享、跨多种微生物有关状况关联,等)。该微生物组特征的识别和表征可以通过降低共病和/或多病的微生物有关状况(例如,其可与环境因素相关联,从而与微生物组相关联,等)的风险和患病率,来促进改进的健康护理的实践(例如,在群体和个体水平上、诸如通过促进诊断和治疗干预等)。Fifth, specific embodiments of the technology can improve at least the technical field of genomics, microbiology, microbiome-related computing, diagnosis, therapy, microbiome-related digital medicine, general digital medicine, modeling and/or other related fields. In one embodiment, the technology can use a set of microbiome characterization modules to model and/or characterize different microbial-related conditions, such as by calculating the identification of relevant microbial features for microbial-related conditions (e.g., it can serve as a biomarker to be used in diagnosis, promote therapeutic intervention, etc.). In another embodiment, the technology can perform cross-condition analysis to identify and evaluate cross-condition microbiome features, which are related to multiple microbial-related conditions (e.g., diseases, phenotypes, etc.) (e.g., shared across multiple microbial-related conditions, associated across multiple microbial-related conditions, etc.). The identification and characterization of the microbiome features can promote the practice of improved health care (e.g., at the population and individual level, such as by promoting diagnostic and therapeutic intervention, etc.) by reducing the risk and prevalence of comorbid and/or multi-disease microbial-related conditions (e.g., it can be associated with environmental factors, thereby associated with the microbiome, etc.).
第六,该技术可以利用专用的计算设备(例如,与诸如下一代测序系统的样品处理系统相关的;与微生物有关表征系统相关联的;与疗法促进系统相关联的系统等)执行与方法100和/或系统200相关联的合适的部分。Sixth, the technology can utilize dedicated computing devices (e.g., systems associated with sample processing systems such as next-generation sequencing systems; systems associated with microbial characterization systems; systems associated with therapy enhancement systems, etc.) to perform appropriate portions associated with method 100 and/or system 200.
然而,在使用非通用计算机系统用于微生物有关表征、微生物组调节和/或用于执行方法100的其他合适部分的情况下,该技术的特定实施例可以提供任何其他合适的益处。However, particular embodiments of the technology may provide any other suitable benefits where a non-general purpose computer system is used for microbe-related characterization, microbiome modulation, and/or for performing other suitable portions of method 100 .
3.系统3. System
如图2所示,系统200的实施方式(例如,用于表征微生物有关状况)可以包括以下任何一个或多个:处理系统(例如,样品处理系统等)210,其可操作以收集和/或处理来自一个或多个用户(例如,人类受试者、患者、动物受试者、环境生态系统、护理提供者等)的生物样品(例如,由用户收集并包括在容器中,该容器包括预处理试剂;等)以确定微生物数据集(例如,微生物遗传序列;微生物序列数据集等);微生物有关表征系统220,其可操作以确定用户微生物组特征(例如,微生物组组成特征;微生物组功能特征;多样性特征;相对丰度范围;诸如基于微生物数据集和/或其他合适的数据;等)、确定微生物有关表征(例如,微生物有关状况表征、疗法有关表征、针对用户的表征,等);和/或疗法促进系统230,其可操作以促进针对一种或多种微生物有关状况(例如,基于一种或多种微生物有关状况;等)的治疗干预(例如,推广疗法,等)。As shown in FIG. 2 , an embodiment of a system 200 (e.g., for characterizing a microbial-related condition) may include any one or more of the following: a processing system (e.g., a sample processing system, etc.) 210 operable to collect and/or process biological samples (e.g., collected by a user and included in a container that includes a pretreatment reagent; etc.) from one or more users (e.g., a human subject, a patient, an animal subject, an environmental ecosystem, a care provider, etc.) to determine a microbial dataset (e.g., a microbial genetic sequence; a microbial sequence dataset, etc.); a microbial-related characterization system 220 operable to determine a user's microbiome characteristics (e.g., a microbiome composition characteristic; a microbiome functional characteristic; a diversity characteristic; a relative abundance range; such as based on a microbial dataset and/or other suitable data; etc.), determine a microbial-related characterization (e.g., a microbial-related condition characterization, a therapy-related characterization, a characterization for a user, etc.); and/or a therapy promotion system 230 operable to promote therapeutic intervention (e.g., promoting therapy, etc.) for one or more microbial-related conditions (e.g., based on one or more microbial-related conditions; etc.).
在特定实施例中,系统200可以包括样品处理系统,该样品处理系统包括:测序系统(例如,下一代测序系统,等),该测序系统可操作以基于与受试者集合相关联的生物样品来确定微生物遗传序列,其中生物样品包括与微生物有关状况相关联的微生物核酸;微生物组表征模块221集合,其可操作以应用分析技术集合,该分析技术包括以下至少两项:统计检验(例如,单变量统计检验等)、降维技术、人工智能方法和/或本文中描述的其他合适方法,并且其中微生物组表征模块221集合包括:第一微生物组表征模块221',其可操作以应用分析技术集合中的第一分析技术(例如,一个或多个单变量统计检验和/或合适的统计检验等),以基于微生物遗传序列确定微生物组特征集合,其中微生物组特征集合与微生物有关状况相关联(例如,与微生物有关状况关联等);和第二微生物组表征模块221”,其可操作以应用分析技术集合中的第二分析技术(例如,降维技术),以基于微生物组特征集合(例如,其中第一微生物组表征模块221'的输出可以串行(serial)、链式(chained)的方式用作第二微生物组表征模块221”的输入,等)确定处理后的微生物组特征集(例如,降维的特征集;包括针对一种或多种微生物有关状况最相关特征的特征集等),其中处理后的微生物组特征集适用于改进微生物有关状况的表征(例如,通过从巨大的潜在特征池识别和利用定制特征的子集来改进准确性、处理速度,从而改进关于微生物有关表征的计算系统的功能、治疗干预促进、和/或本文中描述的其他合适功能等);和其基于处理后的微生物组特征集生成的微生物有关状况模型,其中,微生物有关状况模型可操作以针对用户确定微生物有关状况的表征。In certain embodiments, the system 200 may include a sample processing system, the sample processing system including: a sequencing system (e.g., a next generation sequencing system, etc.), the sequencing system operable to determine a microbial genetic sequence based on a biological sample associated with a subject set, wherein the biological sample includes a microbial nucleic acid associated with a microbial-related condition; a set of microbiome characterization modules 221, which are operable to apply a set of analysis techniques, the analysis techniques including at least two of the following: statistical tests (e.g., univariate statistical tests, etc.), dimensionality reduction techniques, artificial intelligence methods, and/or other suitable methods described herein, and wherein the set of microbiome characterization modules 221 includes: a first microbiome characterization module 221', which is operable to apply a first analysis technique in the set of analysis techniques (e.g., one or more univariate statistical tests and/or suitable statistical tests, etc.) to determine a microbiome feature set based on the microbial genetic sequence, wherein the microbiome feature set is associated with a microbial-related condition (e.g., associated with a microbial-related condition, etc.); and a second microbiome characterization module 221'. A microbiome characterization module 221', which is operable to apply a second analysis technique (e.g., a dimensionality reduction technique) in the set of analysis techniques to determine a processed microbiome feature set (e.g., a reduced feature set; a feature set including the most relevant features for one or more microbiome-related conditions, etc.) based on a microbiome feature set (e.g., wherein the output of the first microbiome characterization module 221' can be used as an input to the second microbiome characterization module 221' in a serial, chained manner, etc.), wherein the processed microbiome feature set is suitable for improving the characterization of microbiome-related conditions (e.g., by identifying and utilizing a subset of customized features from a huge pool of potential features to improve accuracy, processing speed, thereby improving the functionality of a computing system regarding microbiome-related characterization, promotion of therapeutic intervention, and/or other suitable functions described herein, etc.); and a microbiome-related condition model generated based on the processed microbiome feature set, wherein the microbiome-related condition model is operable to determine a characterization of a microbiome-related condition for a user.
系统200的处理系统210可起到接收和/或处理(例如,片段化、扩增、测序、生成相关数据集等)生物样品以将微生物核酸和/或生物样品的其他成分转化为数据(例如,可随后比对(aligned)和分析的遗传序列;微生物数据集等)的作用,来促进微生物有关表征和/或治疗干预的生成。处理系统210可以附加地或可替代地起到诸如通过邮递系统将样品试剂盒250(例如,包括样品容器、用于从一个或多个收集位点收集样品的使用说明等)提供给多个用户(例如,响应于样品试剂盒250的购买订单)的作用。处理系统210可以包括用于测序生物样品(例如,测序来自生物样品的微生物核酸)的一个或多个测序系统215(例如,下一代测序系统,用于靶向扩增子测序、元转录组(metatranscriptomic)测序、元基因组测序、合成测序(sequencing-by-synthesis)技术、毛细管测序技术、桑格(Sanger)测序、焦磷酸测序技术、纳米孔测序技术的测序系统,等),诸如在生成微生物数据(例如,微生物序列数据、用于微生物数据集的其他数据等)中。处理系统210可以附加地或可替代地包括文库制备系统,该文库制备系统可操作来以多重方式自动制备待通过测序系统测序的生物样品(例如,使用与遗传靶标(genetic target)兼容的引物来片段化和扩增,该遗传靶标与微生物有关状况相关联);和/或任何合适的组件。处理系统可以执行本文中描述的任何合适的样品处理技术。然而,处理系统210和相关联组件可以以任何合适的方式配置。The processing system 210 of the system 200 can function to receive and/or process (e.g., fragment, amplify, sequence, generate relevant data sets, etc.) biological samples to convert microbial nucleic acids and/or other components of the biological samples into data (e.g., genetic sequences that can be subsequently aligned and analyzed; microbial data sets, etc.) to facilitate the generation of relevant characterization and/or therapeutic interventions of microorganisms. The processing system 210 can additionally or alternatively function to provide a sample kit 250 (e.g., including a sample container, instructions for collecting samples from one or more collection sites, etc.) to multiple users (e.g., in response to a purchase order for the sample kit 250), such as through a postal system. The processing system 210 may include one or more sequencing systems 215 (e.g., next generation sequencing systems, sequencing systems for targeted amplicon sequencing, metatranscriptomic sequencing, metagenomic sequencing, sequencing-by-synthesis technology, capillary sequencing technology, Sanger sequencing, pyrosequencing technology, nanopore sequencing technology, etc.) for sequencing biological samples (e.g., sequencing microbial nucleic acids from biological samples), such as in generating microbial data (e.g., microbial sequence data, other data for microbial data sets, etc.). The processing system 210 may additionally or alternatively include a library preparation system that is operable to automatically prepare biological samples to be sequenced by the sequencing system in a multiplexed manner (e.g., fragmentation and amplification using primers compatible with a genetic target, the genetic target being associated with a microbial-related condition); and/or any suitable components. The processing system may perform any suitable sample processing technique described herein. However, the processing system 210 and associated components may be configured in any suitable manner.
系统200的微生物组表征系统220可起到确定、分析、表征和/或以其他方式处理微生物数据集(例如,基于导致微生物遗传序列的处理后的生物样品;与参考序列的比对;等)、微生物组特征(例如,个体变量;变量组;与表型预测、与统计描述相关的特征;与从个体获得的样品相关联的变量;与微生物有关状况相关联的变量;以相对或绝对量完整或部分描述样品的微生物组组成和/或功能的变量等)、模型(例如,微生物有关状况模型等)和/或其他合适数据的作用,以促进微生物有关表征和/或治疗干预。在实施例中,微生物组表征系统220可以识别衍生自统计描述与一种或多种微生物有关状况相关联的样品(例如,与微生物有关状况有关的存在、不存在、风险、倾向和/或其他方面相关联的样品,等)之间的差别的特征信息,诸如其中不同的分析可将补充视图提供至区分不同样品(例如,区分与状况的存在或不存在相关的子组,等)的特征中。在特定实施例中,个体预测因子(predictor)、特定生物学过程和/或统计推断的潜在变量可在不同数据复杂性级别提供补充信息,以促进关于表征、诊断和/或治疗的变化的下游机会。在特定实施例中,微生物组表征系统220可以生成和/或应用疗法模型(例如,基于交叉条件分析等),来识别和/或表征用于治疗一种或多种微生物有关状况的疗法。在另一特定实施例中,微生物组表征系统220处理补充数据(例如,要用于改进微生物组表征模块221的应用的先前的知识;诸如与用户、微生物组特征、微生物有关状况、其他成分相关联的先验知识,等)。The microbiome characterization system 220 of the system 200 can function to determine, analyze, characterize, and/or otherwise process microbial data sets (e.g., biological samples based on processing that results in microbial genetic sequences; comparisons with reference sequences; etc.), microbiome features (e.g., individual variables; sets of variables; features associated with phenotypic prediction, statistical descriptions; variables associated with samples obtained from individuals; variables associated with microbial-related conditions; variables that fully or partially describe the microbiome composition and/or function of a sample in relative or absolute quantities, etc.), models (e.g., microbial-related condition models, etc.), and/or other suitable data to facilitate microbial-related characterization and/or therapeutic intervention. In an embodiment, the microbiome characterization system 220 can identify feature information derived from statistical descriptions of differences between samples associated with one or more microbial-related conditions (e.g., samples associated with the presence, absence, risk, tendency, and/or other aspects of microbial-related conditions, etc.), such as where different analyses can provide complementary views into features that distinguish different samples (e.g., distinguishing subgroups associated with the presence or absence of a condition, etc.). In a particular embodiment, individual predictors, specific biological processes, and/or latent variables for statistical inference can provide supplementary information at different data complexity levels to facilitate downstream opportunities for changes in characterization, diagnosis, and/or treatment. In a particular embodiment, the microbiome characterization system 220 can generate and/or apply a therapy model (e.g., based on cross-condition analysis, etc.) to identify and/or characterize therapies for treating one or more microbial-related conditions. In another particular embodiment, the microbiome characterization system 220 processes supplementary data (e.g., prior knowledge to be used to improve the application of the microbiome characterization module 221; such as prior knowledge associated with users, microbiome features, microbial-related conditions, other components, etc.).
微生物组表征系统220优选地包括一个或多个微生物组表征模块221(例如,独立模块、相互依赖的模块等),其可以起到将一种或多种分析技术应用于处理微生物数据集、微生物组特征、补充数据和/或其他合适的数据以促进微生物有关表征和/或治疗干预的作用(例如,如图23所示)。The microbiome characterization system 220 preferably includes one or more microbiome characterization modules 221 (e.g., independent modules, interdependent modules, etc.), which can be used to apply one or more analytical techniques to process microbial datasets, microbiome signatures, supplemental data and/or other suitable data to facilitate microbiome-related characterization and/or therapeutic intervention (e.g., as shown in FIG. 23 ).
任何合适的微生物组表征模块221(例如,利用任何合适的分析技术等)可以以任何合适的方式,以串行(例如,通过链接关于输出和输入的微生物组表征模块221)、同时、重复和/或任何合适的时间关系,以任何合适的组合应用。例如,微生物组表征模块221的输出可以构成微生物有关表征(例如,自身感兴趣的(interest)结果等),其被视为中间成分(例如,用作相同或不同微生物组表征模块221的输入、诸如疗法模型的模型的输入等),和/或被用于任何合适的目的。在特定实施例中,多个微生物组表征模块221可以链接(例如,诸如其中微生物组表征模块221的一个或多个输出可以用作相同或另一微生物组表征模块221的一个或多个输入,等)和/或以其他方式连接(例如,关于数据共享,关于有助于微生物有关表征,关于与一种或多种微生物有关状况的关联等),这可促进一个或多个特征选择(例如,选择微生物组特征的子集以供后续使用等)、特征加权(feature weighting)(例如,用于确定针对不同特征的不同加权,诸如增权或减权(down-weighting)特征,其可以在任何合适的微生物组表征模块221、模型和/或其他合适的过程等中使用,等)、热启动(例如,其中与第一微生物组表征模块221'相关联的输出和/或其他处理可以辅助和/或改进与第二微生物组表征模块221”相关联的处理,诸如关于改进统计学习和/或推断、帮助和/或以其他方式改进与,这可以与促进专注于最相关特征有关,等)。例如,第一微生物组表征模块221'可以(例如,通过应用第一分析技术)确定微生物组特征集合;第二微生物组表征模块221”可以应用(例如,可操作以应用)第二分析技术以执行特征选择、特征加权和热启动中的至少一个,来将微生物组特征集合处理成处理后的微生物组特征集。然而,微生物组表征模块221可以出于任何合适的目的,以任何合适的时间和频率针对任何数量的数据集、用户、微生物有关状况、疗法和/或其他合适的实体应用。Any suitable microbiome characterization module 221 (e.g., using any suitable analysis technique, etc.) can be applied in any suitable manner, in series (e.g., by linking microbiome characterization modules 221 with respect to outputs and inputs), simultaneously, repeatedly, and/or in any suitable temporal relationship, in any suitable combination. For example, the output of a microbiome characterization module 221 can constitute a microbiome-related characterization (e.g., a result of interest itself, etc.), which is considered an intermediate component (e.g., used as an input to the same or different microbiome characterization module 221, an input to a model such as a therapy model, etc.), and/or is used for any suitable purpose. In certain embodiments, multiple microbiome characterization modules 221 can be linked (e.g., such as where one or more outputs of a microbiome characterization module 221 can be used as one or more inputs to the same or another microbiome characterization module 221, etc.) and/or otherwise connected (e.g., with respect to data sharing, with respect to contributing to microbiome-related characterization, with respect to association with one or more microbiome-related conditions, etc.), which can facilitate one or more feature selections (e.g., selecting a subset of microbiome features for subsequent use, etc.), feature weighting (feature weighting, etc.), and/or other features. weighting) (e.g., for determining different weights for different features, such as up-weighting or down-weighting features, which can be used in any suitable microbiome characterization module 221, model and/or other suitable process, etc.), hot start (e.g., where the output and/or other processing associated with the first microbiome characterization module 221' can assist and/or improve the processing associated with the second microbiome characterization module 221", such as with respect to improving statistical learning and/or inference, helping and/or otherwise improving with, which can be related to promoting focus on the most relevant features, etc.). For example, the first microbiome characterization module 221' can determine a microbiome feature set (e.g., by applying a first analysis technique); the second microbiome characterization module 221" can apply (e.g., be operable to apply) a second analysis technique to perform at least one of feature selection, feature weighting, and hot start to process the microbiome feature set into a processed microbiome feature set. However, the microbiome characterization module 221 can be applied for any suitable purpose, at any suitable time and frequency, for any number of data sets, users, microbiome-related conditions, therapies, and/or other suitable entities.
不同的微生物组表征模块221(例如,微生物组表征模块221的不同组合;应用不同分析技术的不同模块;不同的输入和/或输出类型;以诸如关于时间和/或频率的不同方式应用的;等)可以基于以下一项或多项应用(例如,执行、选择、检索、存储等):微生物有关状况(例如,根据所表征的一种或多种微生物有关状况,使用不同组合的微生物组表征模块221,诸如其中不同微生物组表征模块221具有用于处理关于不同微生物有关状况的数据的不同适用性水平,等)、用户(例如,基于不同用户数据和/或特征的不同微生物组表征模块221,该用户数据和/或特征诸如相应样品收集位点、人口统计学、遗传学、环境因素等)、微生物有关表征(例如,用于不同类型的表征、诸如疗法有关表征相对于诊断有关表征的不同微生物组表征模块221,诸如用于相对于确定微生物有关状况的倾向性分值识别相关微生物组组成;等)、疗法(例如,用于监测不同疗法的功效的不同微生物组表征模块221等)、和/或任何其他合适的成分。在实施例中,不同的微生物组表征模块221可针对不同类型的输入、输出、微生物有关表征、微生物有关状况(例如,需要表征的不同表型的测量)、和/或任何其他合适的实体定制。然而,微生物组表征模块221可以以任何合适的方式定制和/或使用,以促进微生物有关表征和/或治疗干预。Different microbiome characterization modules 221 (e.g., different combinations of microbiome characterization modules 221; different modules applying different analysis techniques; different input and/or output types; applied in different ways such as with respect to time and/or frequency; etc.) can be based on one or more of the following applications (e.g., executed, selected, retrieved, stored, etc.): microbiome-related conditions (e.g., using different combinations of microbiome characterization modules 221 depending on one or more microbiome-related conditions being characterized, such as where different microbiome characterization modules 221 have different levels of suitability for processing data about different microbiome-related conditions, etc.), users (e.g., different microbiome characterization modules 221 based on different user data and/or characteristics, such as corresponding sample collection sites, demographics, genetics, environmental factors, etc.), microbiome-related characterizations (e.g., different microbiome characterization modules 221 for different types of characterizations, such as therapy-related characterizations versus diagnosis-related characterizations, such as for identifying relevant microbiome compositions relative to propensity scores for determining microbiome-related conditions; etc.), therapies (e.g., different microbiome characterization modules 221 for monitoring the efficacy of different therapies, etc.), and/or any other suitable components. In an embodiment, different microbiome characterization modules 221 can be customized for different types of inputs, outputs, microbe-related characterizations, microbe-related conditions (e.g., measurements of different phenotypes that need to be characterized), and/or any other suitable entities. However, the microbiome characterization modules 221 can be customized and/or used in any suitable manner to facilitate microbe-related characterizations and/or therapeutic interventions.
系统200的微生物组表征模块221、模型、其他组件和/或方法100的合适部分(例如,确定微生物组特征、确定微生物有关表征等)可以采用包括以下任何一项或多项的分析技术:统计检验(例如,单变量统计检验、多变量统计检验等)、降维技术、人工智能方法(例如,机器学习方法等)、对数据执行模式识别(例如,识别微生物有关状况与微生物组特征之间的关联性等)、融合来自多个源的数据(例如,基于来自与一种或多种微生物有关状况相关联的多个用户的微生物组数据和/或补充数据、诸如基于从数据提取的微生物组特征生成表征模型等)、值(例如,平均值等)的组合、压缩、转换(例如,数模转换,模数转换)、对数据执行统计估计(例如,普通最小二乘回归、非负最小二乘回归、主成分分析、岭回归等)、波调制、标准化、更新(例如,基于处理过的生物样品随时间推移的表征模型和/或疗法模型的更新;等)、排名(例如,微生物组特征;疗法;等)、加权(例如,微生物组特征等)、验证、过滤(例如,用于基线校正、数据裁剪等)、降噪、平滑、填充(例如,间隙填充)、对齐、模型拟合、分箱(binning)、加窗、剪辑(clipping)、变换、数学运算(例如,导数,移动平均值,求和,减法,相乘,除法,等)、数据关联、复用、解复用、内插、外推、聚类分析(clustering)、图像处理技术、其他信号处理操作、其他图像处理操作、可视化和/或任何其他合适的处理操作。人工智能方法可以包括以下任一项或多项:监督学习(例如,使用逻辑回归、使用反向传播神经网络、使用随机森林、决策树等)、无监督学习(例如,使用先验(Apriori)算法、使用K均值聚类分析)、半监督学习、深度学习算法(例如,神经网络、受限玻尔兹曼(Boltzmann)机、深度信念网络方法、卷积(convolutional)神经网络方法、递归(recurrent)神经网络方法、堆叠式自动编码器方法等)、强化学习(例如,使用Q学习算法、使用时间差学习)、回归算法(例如,普通最小二乘法、逻辑回归、逐步回归、多变量自适应回归样条(multivariate adaptiveregression splines)、局部估计散点平滑(locally estimated scatterplot smoothing)等)、基于实例的方法(例如,k最近邻、学习矢量量化、自组织映射等)、正则化方法(例如,岭回归、最小绝对收缩和选择算子(operator)、弹性网(elastic net),等)、决策树学习方法(例如,分类树和回归树、迭代二分法3(iterative dichotomiser3)、C4.5、卡方自动交互检测、决策树桩、随机森林、多变量自适应回归样条曲线、梯度提升机(gradient boostingmachines)等)、贝叶斯(Bayesian)方法(例如,朴素贝叶斯(naive Bayes)、平均单一依赖估计量(averaged one-dependence estimatiors)、贝叶斯信念网络等)、核方法(例如,支持矢量机、径向基函数、线性判别分析等)、聚类分析方法(例如k均值聚类分析、期望最大化等)、关联规则学习算法(例如,先验算法、深度优先(Eclat)算法等)、人工神经网络模型(例如,感知器(Perceptron)方法、反向传播方法、霍普菲尔德(Hopfield)网络方法、自组织映射方法,学习矢量量化方法等)、整合方法(例如,增强、自举聚合(boostrappedaggregation)、自适应增强(AdaBoost)、堆叠泛化、梯度提升机、随机森林方法等)和/或任何合适的人工智能方法。然而,可以以任何合适的方式采用数据处理。The microbiome characterization module 221 of the system 200, the model, other components and/or appropriate parts of the method 100 (e.g., determining microbiome features, determining microbiome-related features, etc.) can use any one or more of the following analysis techniques: statistical tests (e.g., univariate statistical tests, multivariate statistical tests, etc.), dimensionality reduction techniques, artificial intelligence methods (e.g., machine learning methods, etc.), performing pattern recognition on data (e.g., identifying the association between microbiome-related conditions and microbiome features, etc.), fusing data from multiple sources (e.g., based on microbiome data and/or supplementary data from multiple users associated with one or more microbiome-related conditions, such as generating a characterization model based on microbiome features extracted from the data, etc.), combining values (e.g., average values, etc.), compression, conversion (e.g., digital-to-analog conversion, analog-to-digital conversion), performing statistical estimation on data (e.g., general least squares regression, non-negative least squares regression, principal component analysis, ridge regression, etc.), wave modulation, normalization, updating (e.g., updating of characterization models and/or therapy models based on treated biological samples over time; etc.), ranking (e.g., microbiome features; therapies; etc.), weighting (e.g., microbiome features, etc.), validation, filtering (e.g., for baseline correction, data clipping, etc.), noise reduction, smoothing, filling (e.g., gap filling), alignment, model fitting, binning, windowing, clipping, transformation, mathematical operations (e.g., derivatives, moving averages, summation, subtraction, multiplication, division, etc.), data association, multiplexing, demultiplexing, interpolation, extrapolation, clustering, image processing techniques, other signal processing operations, other image processing operations, visualization, and/or any other suitable processing operation. Artificial intelligence methods may include any one or more of the following: supervised learning (e.g., using logistic regression, using back-propagation neural networks, using random forests, decision trees, etc.), unsupervised learning (e.g., using an Apriori algorithm, using K-means cluster analysis), semi-supervised learning, deep learning algorithms (e.g., neural networks, restricted Boltzmann machines, deep belief network methods, convolutional neural network methods, recurrent neural network methods, stacked autoencoder methods, etc.), reinforcement learning (e.g., using a Q-learning algorithm, using temporal difference learning), regression algorithms (e.g., ordinary least squares, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing, etc.), instance-based methods (e.g., k-nearest neighbors, learning vector quantization, self-organizing maps, etc.), regularization methods (e.g., ridge regression, least absolute shrinkage and selection operators, elastic nets, etc.), net), decision tree learning methods (e.g., classification and regression trees, iterative dichotomiser3, C4.5, chi-square automatic interaction detection, decision stumps, random forests, multivariate adaptive regression splines, gradient boosting machines, etc.), Bayesian methods (e.g., naive Bayes, averaged one-dependence estimator, etc.), estimatiors, Bayesian belief networks, etc.), kernel methods (e.g., support vector machines, radial basis functions, linear discriminant analysis, etc.), clustering analysis methods (e.g., k-means clustering analysis, expectation maximization, etc.), association rule learning algorithms (e.g., a priori algorithms, depth-first (Eclat) algorithms, etc.), artificial neural network models (e.g., perceptron methods, back-propagation methods, Hopfield network methods, self-organizing mapping methods, learning vector quantization methods, etc.), integration methods (e.g., enhancement, boostrapped aggregation, adaptive enhancement (AdaBoost), stacked generalization, gradient boosting machines, random forest methods, etc.) and/or any suitable artificial intelligence methods. However, data processing can be adopted in any suitable manner.
在第一变型中,如图10所示,微生物组表征模块221(例如,分析模块A222)可以应用一个或多个统计检验(例如,单变量统计检验、多变量等),该统计检验可以包括t检验、柯尔莫哥洛夫-斯米尔诺夫(Kolmogorov-Smirnov)检验、回归模型和/或与统计检验有关的其他合适技术中的任何一项或多项。微生物组表征模块221可以应用统计检验来确定微生物组特征集合(例如,基于诸如包括微生物遗传序列的微生物数据集;基于先验知识,诸如微生物组特征与微生物有关状况之间的关联,表示受试者、用户有用信息的补充数据;等)。微生物组表征模块221可以应用多个统计检验(例如,单变量统计检验、多变量等),其可以通过采用不同的建模策略来相互补充,例如用于检测均值和方差的变化、或者存在和/或不存在模式。在一实施例中,不同类型的统计检验(例如,单变量统计检验、多变量等)(和/或其他合适的分析技术)的输出(例如,结果)可以结合、分组和/或以其他方式聚合,以便显示不同分析技术(例如,如图18所示,表明了部分A和部分C中不同的单一检验、和来自关于部分B的多重检验的输出并集(union))之间的关联(例如,相似性,差异)、诸如关于所识别的微生物组特征。在特定实施例中,第一微生物组表征模块221可以应用(例如,可操作以应用等)第一统计检验(例如,单变量统计检验等)以确定第一微生物组特征集合,第二微生物组表征模块221”(和/或使用相同的第一微生物组表征模块221')可以应用第二统计检验(例如,第二单变量统计检验等)以确定第二微生物组特征集合。来自多种分析技术输出的聚合可以包括来自不同分析技术不同输出之间的交集或并集,其中利用这些聚合的输出可用于实现特异性和敏感性的目标平衡(例如,较高的特异性与较低的敏感性;较高的敏感性与较低的特异性等)。任何适合的微生物数据集、微生物组表征模块221的输入和/或输出、和/或其他适合的数据可以用作输入,或者可以用作统计检验的输出,并且微生物组表征模块221的输出可以用作用于任何其他合适的微生物组表征模块221的输入。然而,微生物组表征模块221(例如,分析模块A222)可以以任何合适的方式配置。In a first variation, as shown in FIG10 , the microbiome characterization module 221 (e.g., analysis module A222) can apply one or more statistical tests (e.g., univariate statistical tests, multivariate, etc.), which can include any one or more of a t-test, a Kolmogorov-Smirnov test, a regression model, and/or other suitable techniques related to statistical tests. The microbiome characterization module 221 can apply statistical tests to determine a microbiome feature set (e.g., based on a microbial data set such as a microbial genetic sequence; based on prior knowledge, such as an association between microbiome features and microbial-related conditions, supplementary data representing useful information for subjects and users; etc.). The microbiome characterization module 221 can apply multiple statistical tests (e.g., univariate statistical tests, multivariate, etc.), which can complement each other by adopting different modeling strategies, such as for detecting changes in means and variances, or the presence and/or absence of patterns. In one embodiment, the outputs (e.g., results) of different types of statistical tests (e.g., univariate statistical tests, multivariate, etc.) (and/or other suitable analysis techniques) can be combined, grouped and/or otherwise aggregated to display associations (e.g., similarities, differences) between different analysis techniques (e.g., as shown in Figure 18, showing different single tests in Part A and Part C, and the union of outputs from multiple tests on Part B), such as with respect to identified microbiome features. In certain embodiments, the first microbiome characterization module 221 may apply (e.g., be operable to apply, etc.) a first statistical test (e.g., a univariate statistical test, etc.) to determine a first microbiome feature set, and the second microbiome characterization module 221" (and/or using the same first microbiome characterization module 221') may apply a second statistical test (e.g., a second univariate statistical test, etc.) to determine a second microbiome feature set. Aggregation from outputs of multiple analysis techniques may include an intersection or union between different outputs from different analysis techniques, wherein the outputs of these aggregations may be used to achieve a target balance of specificity and sensitivity (e.g., higher specificity with lower sensitivity; higher sensitivity with lower specificity, etc.). Any suitable microbial data set, input and/or output of a microbiome characterization module 221, and/or other suitable data may be used as an input, or may be used as an output of a statistical test, and the output of a microbiome characterization module 221 may be used as an input for any other suitable microbiome characterization module 221. However, the microbiome characterization module 221 (e.g., analysis module A222) may be configured in any suitable manner.
在第二变型中,如图11所示,微生物组表征模块221(例如,分析模块B223)可以应用一种或多种降维技术,该降维技术包括以下任何一项或多项:有监督降维技术;无监督降维技术;缺失值比率;主成分分析(principal component analysis,PCA);概率PCA;矩阵分解技术;诸如潜在狄利克雷(dirichlet)分布或分层狄利克雷过程的组成混合物模型(compositional mixtures models);如等距映射(isomap)或局部线性嵌入、局部最小二乘回归、萨蒙(Sammon)映射、多维缩放、投影追踪的特征嵌入技术;和/或与降维有关的任何其他合适技术。应用降维技术可以减少数据集中的维数(例如,特征、样品等)。任何合适的微生物数据集、微生物组表征模块221的输入和/或输出、和/或其他合适的数据可以用作输入,或者可以为降维技术的输出(例如,使用由统计检验确定的微生物组特征作为降维技术的输入来减少特征数量等),并且微生物组表征模块221的输出可用作任何其他合适的微生物组表征模块221的输入(例如,用于统计检验;诸如随机森林、核机器、支持矢量机、回归方法的人工智能方法;分析模块A222;分析模块C224等)。应用微生物组表征模块221可以促进确定推断的潜在特征和表型有关数据之间的线性或非线性关联,该表型有关数据与一种或多种微生物有关状况相关联。微生物组表征模块221的输出可以包括微生物有关表征(例如,自身感兴趣的结果)、用于附加分析的输出(例如,通过提供具有预测值的个体特征和/或对于聚类和分类样品有用的潜在特征,等),和/或用于任何合适的目的。然而,微生物组表征模块221(例如,分析模块B223)可以以任何合适的方式配置。In a second variation, as shown in FIG11 , the microbiome characterization module 221 (e.g., analysis module B223) may apply one or more dimensionality reduction techniques, including any one or more of the following: supervised dimensionality reduction techniques; unsupervised dimensionality reduction techniques; missing value ratios; principal component analysis (PCA); probabilistic PCA; matrix decomposition techniques; compositional mixtures models such as latent Dirichlet distribution or hierarchical Dirichlet process; feature embedding techniques such as isomap or local linear embedding, local least squares regression, Sammon mapping, multidimensional scaling, projection pursuit; and/or any other suitable techniques related to dimensionality reduction. Applying dimensionality reduction techniques may reduce the number of dimensions (e.g., features, samples, etc.) in a data set. Any suitable microbial data set, input and/or output of the microbiome characterization module 221, and/or other suitable data can be used as input, or can be the output of a dimensionality reduction technique (e.g., using microbiome features determined by statistical tests as inputs to dimensionality reduction techniques to reduce the number of features, etc.), and the output of the microbiome characterization module 221 can be used as input to any other suitable microbiome characterization module 221 (e.g., for statistical tests; artificial intelligence methods such as random forests, kernel machines, support vector machines, regression methods; analysis modules A222; analysis modules C224, etc.). Applying the microbiome characterization module 221 can facilitate determining a linear or nonlinear association between inferred potential features and phenotype-related data, which is associated with one or more microbial-related conditions. The output of the microbiome characterization module 221 can include microbial-related characterizations (e.g., results of interest in themselves), outputs for additional analysis (e.g., by providing individual features with predictive value and/or potential features useful for clustering and classifying samples, etc.), and/or for any suitable purpose. However, the microbiome characterization module 221 (e.g., analysis module B223) can be configured in any suitable manner.
在第三变型中,如图12所示,微生物组表征模块221(例如,分析模块C224)可以促进一种或多种机器学习模型(和/或其他合适的人工智能方法)的应用。在实施例中,微生物组表征模块221可以起到指导人工智能方法(例如,神经网络,自动编码器模型或生成对抗网络,等)的构架和/或参数估计的作用,诸如例如通过编码表型和/或其他微生物有关状况的非线性预测功能来指导。任何合适的微生物数据集、微生物组表征模块221的输入和/或输出、和/或其他合适的数据可以用作输入,或者可以为输出(例如,使用统计检验的输出、降维方法的输出、分析模块A222的输出、分析模块B223的输出、和/或使用任何合适的数据作为输入,等),并且微生物组表征模块221的输出可用作任何其他合适的微生物组表征模块221的输入。微生物组表征模块221的输出可以包括微生物有关表征(例如,诸如微生物有关状况的倾向性分值的表型预测等)、用于附加分析的输出(例如,用于描述预测值的特征的相关性分值,其可用于识别与表型预测和/或其他类型的预测最相关的特征,等),和/或可用于任何合适的目的。然而,微生物组表征模块221(例如,分析模块C224)可以以任何合适的方式配置。In a third variation, as shown in FIG12 , the microbiome characterization module 221 (e.g., analysis module C224) can facilitate the application of one or more machine learning models (and/or other suitable artificial intelligence methods). In an embodiment, the microbiome characterization module 221 can serve to guide the framework and/or parameter estimation of an artificial intelligence method (e.g., a neural network, an autoencoder model or a generative adversarial network, etc.), such as, for example, by guiding the nonlinear prediction function of encoding phenotypes and/or other microbial related conditions. Any suitable microbial data set, input and/or output of the microbiome characterization module 221, and/or other suitable data can be used as input, or can be output (e.g., using the output of a statistical test, the output of a dimensionality reduction method, the output of an analysis module A222, the output of an analysis module B223, and/or using any suitable data as input, etc.), and the output of the microbiome characterization module 221 can be used as the input of any other suitable microbiome characterization module 221. The output of the microbiome characterization module 221 may include microbiome-related characterizations (e.g., phenotypic predictions such as propensity scores for microbiome-related conditions, etc.), outputs for additional analysis (e.g., correlation scores for features describing predictive values, which can be used to identify features most relevant to phenotypic predictions and/or other types of predictions, etc.), and/or may be used for any suitable purpose. However, the microbiome characterization module 221 (e.g., analysis module C224) can be configured in any suitable manner.
在第四变型中,如图13所示,微生物组表征模块221(例如,分析模块D225)可以将一种或多种分析技术(例如,通过回归和/或等效方法的交互作用的二阶或更高阶测试;诸如随机森林和/或支持矢量机、数据压缩技术的机器学习算法;核机器等)应用于检测微生物数据(例如,不同的微生物组组成概况(profiles)等)、微生物组特征和/或从微生物组特征的转变(例如,比率、乘积、从降维算法的应用中获得的特征,等)获得的特征之间的统计交互作用。然而,微生物组表征模块221(例如,分析模块D225)可以以任何合适的方式配置。In a fourth variation, as shown in FIG13 , the microbiome characterization module 221 (e.g., analysis module D225) may apply one or more analysis techniques (e.g., second-order or higher-order tests of interactions by regression and/or equivalent methods; machine learning algorithms such as random forests and/or support vector machines, data compression techniques; kernel machines, etc.) to detect statistical interactions between microbial data (e.g., different microbiome composition profiles, etc.), microbiome features, and/or features obtained from transformations of microbiome features (e.g., ratios, products, features obtained from the application of dimensionality reduction algorithms, etc.). However, the microbiome characterization module 221 (e.g., analysis module D225) may be configured in any suitable manner.
在第五变型中,如图14所示,微生物组表征模块221(例如,分析模块E226)可以确定表型预测、风险指数、倾向性分值、其他指数和/或与微生物有关状况相关联的(例如,与针对用户诊断微生物有关状况相关联的等)其他合适指标,诸如通过应用包括以下至少一项或多项的分析技术:统计检验(例如,单变量统计检验、多变量统计检验等)、单变量技术、多变量技术、人工智能方法(例如,机器学习模型等)和/或其他合适的技术(例如,其中输出可用作微生物组组成、功能和/或与微生物有关状况相关联的其他合适的微生物组有关方面的总结(summary))。微生物组表征模块221可以诸如通过使用实证分析(empiricalanalyses)的标准化技术,来定义输出范围的最小值和/或最大值。在一实施例中,可以针对参考样品集合(例如,针对对应于参考样品的数据等)计算分值,其中可以记录和使用最小的和最大的观测值,从而根据将特定样品(例如,后续样品)的分值标准化,这可以促进分值处于0到1的范围。附加地或可替代地,微生物组表征模块221可以(例如,以在表征、诊断和/或治疗指导中的可识别值,等)确定校准分值。在一实施例中,微生物组表征模块221可以通过针对样品集合(例如,对应于健康受试者和具有一种或多种感兴趣的微生物有关状况的受试者)确定分值(例如,倾向性分值等);通过针对倾向性分值(例如,10)、具有一种或多种感兴趣的微生物有关状况的受试者分数(fraction)(例如,患病受试者的#/(患病受试者的#+健康受试者的#))的每个可能值计算将倾向性分值转换为校准分值(例如,处于0到1的范围),分值数值(score value)大于或等于校准分值,其中并且其中这可以被视为将患病个体的分数的概率密度函数作为倾向性分值数值的函数进行估计。然而,微生物组表征模块221(例如,分析模块E226)可以以任何合适的方式配置。In a fifth variation, as shown in FIG. 14 , the microbiome characterization module 221 (e.g., analysis module E226) can determine phenotypic predictions, risk indices, propensity scores, other indices, and/or other suitable indicators associated with microbiome-related conditions (e.g., associated with diagnosing microbiome-related conditions for a user, etc.), such as by applying an analysis technique comprising at least one or more of the following: statistical tests (e.g., univariate statistical tests, multivariate statistical tests, etc.), univariate techniques, multivariate techniques, artificial intelligence methods (e.g., machine learning models, etc.), and/or other suitable techniques (e.g., where the output can be used as a summary of microbiome composition, function, and/or other suitable microbiome-related aspects associated with microbiome-related conditions). The microbiome characterization module 221 can define a minimum and/or maximum value for the output range, such as by using a standardized technique of empirical analyses. In one embodiment, a score can be calculated for a reference sample set (e.g., for data corresponding to a reference sample, etc.), where the minimum and maximum observed values can be recorded and used, thereby determining the minimum and maximum values of the output range. The scores for a particular sample (e.g., a subsequent sample) are normalized, which can facilitate scores in the range of 0 to 1. Additionally or alternatively, the microbiome characterization module 221 can determine a calibration score (e.g., with a recognizable value in characterization, diagnosis, and/or treatment guidance, etc.). In one embodiment, the microbiome characterization module 221 can determine a score (e.g., a propensity score, etc.) for a sample set (e.g., corresponding to healthy subjects and subjects with one or more microbial-related conditions of interest); convert the propensity score to a calibration score (e.g., in the range of 0 to 1) by calculating for each possible value of the propensity score (e.g., 10), the fraction of subjects with one or more microbial-related conditions of interest (e.g., # of diseased subjects/(# of diseased subjects + # of healthy subjects)), the score value is greater than or equal to the calibration score, wherein And where this can be viewed as estimating a probability density function of the fraction of diseased individuals as a function of the propensity score values. However, the microbiome characterization module 221 (eg, analysis module E 226 ) can be configured in any suitable manner.
在第六变型中,如图15所示,微生物组表征模块221(例如,分析模块F226)可以将微生物组特征(例如,微生物组特征和微生物有关状况之间的关联、与用户特性的关联等)、微生物有关状况、用户、微生物数据集和/或其他合适的成分的先验知识(例如,生物学数据,用户数据,等),应用于改进与其他微生物组表征模块221(例如,分析模块A222、分析模块B223、分析模块C 224等)相关联的处理。在一实施例中,微生物组表征模块221可以将统计推断朝向具有较低错误率的改进的预测模型引导,从而改进计算系统的功能。在实施例中,可以通过利用硬特征(hard features)、过滤、加权方案、包括数据建模步骤中的外部变量、其他分析技术和/或任何其他合适的过程,来执行该知识(例如,先验信息,等)的包含(inclusion)。然而,微生物组表征模块221(例如,分析模块F226)可以任何合适的方式配置。In a sixth variation, as shown in FIG. 15 , a microbiome characterization module 221 (e.g., analysis module F226) may apply prior knowledge of microbiome features (e.g., associations between microbiome features and microbiome-related conditions, associations with user characteristics, etc.), microbiome-related conditions, users, microbiome data sets, and/or other suitable components (e.g., biological data, user data, etc.) to improve processing associated with other microbiome characterization modules 221 (e.g., analysis module A 222, analysis module B 223, analysis module C 224, etc.). In one embodiment, the microbiome characterization module 221 may guide statistical inference toward an improved prediction model with a lower error rate, thereby improving the functionality of the computing system. In an embodiment, the inclusion of this knowledge (e.g., prior information, etc.) may be performed by utilizing hard features, filtering, weighting schemes, including external variables in the data modeling step, other analysis techniques, and/or any other suitable process. However, the microbiome characterization module 221 (e.g., analysis module F226) may be configured in any suitable manner.
在第七变型中,如图16所示,微生物组表征模块221(例如,分析模块G227)可以处理被识别为与一种或多种微生物有关状况统计相关联的特征,以和其他特征对比,该其他特征不与一种或多种微生物有关状况相关联,例如识别在被发现与一种或多种微生物有关状况相关联或不相关联的那些特征中或多或少共同的总体特征。微生物组表征模块221可以生成和/或将映射(例如,微生物组特征的映射等)利用到诸如基因调控网络或生化途径的生物注释。然而,微生物组表征模块221(例如,分析模块G 227)可以以任何合适的方式配置。In a seventh variation, as shown in FIG16 , the microbiome characterization module 221 (e.g., analysis module G 227) can process features identified as being statistically associated with one or more microbial-related conditions to compare with other features that are not associated with one or more microbial-related conditions, such as identifying more or less common overall features among those features that are found to be associated or not associated with one or more microbial-related conditions. The microbiome characterization module 221 can generate and/or utilize mappings (e.g., mappings of microbiome features, etc.) to biological annotations such as gene regulatory networks or biochemical pathways. However, the microbiome characterization module 221 (e.g., analysis module G 227) can be configured in any suitable manner.
如图17所示,微生物组表征系统220可以优选地执行从多个位点收集的相关联样品的多位点分析(例如,基于与不同收集位点相关联的多位点微生物数据集,用微生物组表征模块221执行多位点分析;基于微生物组表征模块221的输出生成多位点表征;等)。位点(例如,收集位点等)可以包括以下任何一个或多个区域:肠道、皮肤、鼻、口、生殖器、其他合适的生理位点、其他样品收集位点和/或任何其他合适的位点。可以在群体水平(例如,关于用于识别微生物组特征和/或生成诸如不同模型的相关联模型的不同群体,定制该不同模型以分析与多个收集位点相关联的数据集,等)、个体水平(例如,针对用户)上、和/或针对任何合适的实体,执行多位点分析。可以使用和/或基于一个或多个微生物组表征模块221(例如,基于其输出等)和/或任何其他合适的组件(例如,远程计算系统、用户设备等)来执行多位点分析。例如,系统200可以包括:样品处理网络,其可操作以处理(例如,收集、测序等)包括从多个收集位点收集的位点多样性样品的生物样品,该收集位点包括肠道、生殖器、口、皮肤和鼻中的至少两个;和第一微生物组表征模块221,其可操作以应用第一统计检验(例如,单变量统计检验等)(和/或其他合适的分析技术),以基于位点多样性样品确定微生物组特征集合的微生物组特征的第一子集,其中来自微生物组特征的第一子集的微生物组特征的各子集对应于来自多个收集位点的不同收集位点(例如,基于针对不同收集位点的不同微生物组组成和/或功能的针对不同收集位点的不同或相似类型的微生物组特征,等)。在该实施例中,系统200可以包括第二微生物组表征模块221,其可操作以应用附加的统计检验(例如,单变量统计检验;与第一统计检验相比不同类型的统计检验,例如不同的单变量统计检验;等)以基于位点多样性样品确定微生物组特征集合的微生物组特征的第二子集(例如,其中微生物组特征的第一子集对应于第一统计检验,并且其中第一子集的不同子集对应于不同的收集位点;其中微生物组特征的第二子集对应于附加的统计检验,并且其中第二子集的不同子集对应于不同的收集位点;等),并且其中基于微生物组特征的第一子集和第二子集生成微生物有关状况模型(例如,用于多位点分析的模型;其中可以基于微生物组特征生成多个微生物有关状况模型,诸如针对不同收集位点和/或针对与不同收集位点相关联的不同微生物有关状况的不同模型,等)。As shown in FIG. 17 , the microbiome characterization system 220 may preferably perform multi-site analysis of associated samples collected from multiple sites (e.g., performing multi-site analysis with a microbiome characterization module 221 based on a multi-site microbial dataset associated with different collection sites; generating a multi-site characterization based on the output of the microbiome characterization module 221; etc.). Sites (e.g., collection sites, etc.) may include any one or more of the following areas: intestinal tract, skin, nose, mouth, genitals, other suitable physiological sites, other sample collection sites, and/or any other suitable sites. Multi-site analysis may be performed at a population level (e.g., with respect to different populations for identifying microbiome features and/or generating associated models such as different models, customizing the different models to analyze datasets associated with multiple collection sites, etc.), at an individual level (e.g., for a user), and/or for any suitable entity. Multi-site analysis may be performed using and/or based on one or more microbiome characterization modules 221 (e.g., based on their output, etc.) and/or any other suitable component (e.g., a remote computing system, a user device, etc.). For example, system 200 may include: a sample processing network operable to process (e.g., collect, sequence, etc.) biological samples including site-diversity samples collected from multiple collection sites, the collection sites including at least two of the intestine, genitals, mouth, skin, and nose; and a first microbiome characterization module 221 operable to apply a first statistical test (e.g., a univariate statistical test, etc.) (and/or other suitable analytical techniques) to determine a first subset of microbiome features of a microbiome feature set based on the site-diversity samples, wherein each subset of microbiome features from the first subset of microbiome features corresponds to a different collection site from the multiple collection sites (e.g., different or similar types of microbiome features for different collection sites based on different microbiome compositions and/or functions for different collection sites, etc.). In this embodiment, the system 200 may include a second microbiome characterization module 221 that is operable to apply an additional statistical test (e.g., a univariate statistical test; a different type of statistical test compared to the first statistical test, such as a different univariate statistical test; etc.) to determine a second subset of microbiome features of the microbiome feature set based on the site diversity sample (e.g., wherein the first subset of microbiome features corresponds to the first statistical test, and wherein different subsets of the first subset correspond to different collection sites; wherein the second subset of microbiome features corresponds to the additional statistical test, and wherein different subsets of the second subset correspond to different collection sites; etc.), and wherein a microbiome-related condition model is generated based on the first subset and the second subset of microbiome features (e.g., a model for multi-site analysis; wherein multiple microbiome-related condition models can be generated based on the microbiome features, such as different models for different collection sites and/or for different microbiome-related conditions associated with different collection sites, etc.).
多位点分析可以包括位点方面(site-wise)表征的整合、组合和/或以其他方式聚合位点方面表征(例如,从不同微生物数据集计算的不同位点方面个体倾向性分值、该不同微生物数据集对应于在不同收集位点处收集的样品,等)、位点方面治疗干预促进、和/或在多位点分析的情况下的任何其他合适过程。可以通过应用以下至少一项或多项来执行多位点分析(例如,使用微生物组表征模块221等):包括处理分值或概率的贝叶斯和频率论(Frequentist)方法的统计技术,和/或其他合适的分析技术。在变型中,可以组合与(例如,单个用户的、多个用户等的)不同收集位点相关联的个体指标(例如,用于一种或多种微生物有关状况的倾向性分值和/或其他指标)以例如通过使用个体指标值的平均值来确定总体指标(例如,总体疾病倾向性分值和/或其他指标,等)。可以使用标准公式来计算标准偏差,以将不确定度从个体位点方面数据(例如,针对个体的个体倾向性分值等)传播到总体指标(例如,总体疾病倾向性分值等)中。在实施例中,总体指标(例如,多位点表征等)可以描述相对任何单个位点方面指标的附加信息,并且其中位点方面指标可以提供互补的和非冗余的信息。在特定实施例中,互补性可以表明对应于不同位点的微生物组有关表征(例如,指标等)不完全关联(例如,微生物组组成、功能和/或其他合适的表征的一个位点不能完美地预测其他位点的微生物组组成、功能和/或其他合适的表征,等)。多位点分析可以说明采样位点之间信息的冗余性(例如,其中不这样做可能导致有偏差的总体指标,例如通过向它们之间具有强关联性的位点给予高度重视(importance),等)。在一个变型中,微生物组表征系统220可以使用关于采样之间(例如,在对应于不同位点多样性样品的微生物数据集之间,等)的协方差/关联性的信息,该信息可以从相应的数据估计,诸如用以确定改进的总体指标(例如,具有增加的准确性等)。在一实施例中,可以多变量统计方法(例如,用于估计协方差和/或关联性等),应用于解释非冗余信息。在一特定实施例中,可以使用对应于正在考虑的位点的微生物组特征(例如,微生物组组成、微生物组功能、微生物组特征、微生物数据集、微生物组概况的其他合适的方面,等)之间的特定协方差/关联性模式来估计均值和标准偏差。均值和方差可以通过和来估计,S是正在考虑的位点数,xi是位点方面分值,并且其中σi和σij分别是第i个位点方面分值的方差和第i个位点与第j个位点之间的协方差参数。这些协方差和/或关联性的估计可以使用多变量统计方法来执行。在一特定实施例中,对于具有多位点微生物数据的用户,微生物组表征系统220可以:诸如通过使用PCA并选择足以表征数据的潜在变量的子集,将降维技术分别应用于各位点的数据;和/或用来自各位点的潜在变量,可以使用多变量方法、例如通过使用典型关联分析,来估计协方差/关联性,但是任何合适的分析技术和/或微生物组表征模块221可以用于多位点分析。Multi-site analysis may include integration, combination, and/or otherwise aggregation of site-wise characterizations (e.g., different site-wise individual propensity scores calculated from different microbial data sets, the different microbial data sets corresponding to samples collected at different collection sites, etc.), site-wise therapeutic intervention promotion, and/or any other suitable process in the case of multi-site analysis. Multi-site analysis (e.g., using microbiome characterization module 221, etc.) may be performed by applying at least one or more of the following: statistical techniques including Bayesian and frequentist methods for processing scores or probabilities, and/or other suitable analysis techniques. In a variation, individual indicators (e.g., propensity scores and/or other indicators for one or more microbial-related conditions) associated with different collection sites (e.g., of a single user, multiple users, etc.) may be combined to determine an overall indicator (e.g., an overall disease propensity score and/or other indicator, etc.), for example, by using an average of the individual indicator values. Standard deviations can be calculated using standard formulas to propagate uncertainty from individual site-related data (e.g., individual propensity scores for individuals, etc.) to overall indicators (e.g., overall disease propensity scores, etc.). In an embodiment, an overall indicator (e.g., multi-site characterization, etc.) can describe additional information relative to any single site-related indicator, and wherein the site-related indicator can provide complementary and non-redundant information. In a specific embodiment, complementarity can indicate that microbiome-related characterizations (e.g., indicators, etc.) corresponding to different sites are not completely associated (e.g., one site of microbiome composition, function, and/or other suitable characterizations cannot perfectly predict the microbiome composition, function, and/or other suitable characterizations of other sites, etc.). Multi-site analysis can account for the redundancy of information between sampling sites (e.g., where failure to do so may result in a biased overall indicator, such as by giving high importance to sites with strong associations between them, etc.). In one variation, the microbiome characterization system 220 can use information about covariance/correlation between sampling (e.g., between microbiome datasets corresponding to samples of different site diversity, etc.), which can be estimated from the corresponding data, such as to determine an improved overall metric (e.g., with increased accuracy, etc.). In one embodiment, multivariate statistical methods (e.g., for estimating covariance and/or correlation, etc.) can be applied to interpret non-redundant information. In a particular embodiment, a particular covariance/correlation pattern between microbiome features (e.g., microbiome composition, microbiome function, microbiome features, microbiome datasets, other suitable aspects of a microbiome profile, etc.) corresponding to the site being considered can be used to estimate the mean and standard deviation. The mean and variance can be obtained by and to estimate, S is the number of sites under consideration, xi is the site aspect score, and where σi and σij are the variance of the i-th site aspect score and the covariance parameter between the i-th site and the j-th site, respectively. These estimates of covariance and/or associations can be performed using multivariate statistical methods. In a particular embodiment, for users with multi-site microbial data, the microbiome characterization system 220 can: apply dimensionality reduction techniques to the data of each site separately, such as by using PCA and selecting a subset of latent variables sufficient to characterize the data; and/or using the latent variables from each site, covariance/association can be estimated using multivariate methods, such as by using canonical association analysis, but any suitable analysis technique and/or microbiome characterization module 221 can be used for multi-site analysis.
在一特定实施例中,如图17所示,可以通过以下一项或多项来确定总体倾向性分值(例如,针对一种或多种微生物有关状况):从两个以上收集位点收集来自用户的样品;确定多位点微生物数据集(例如,包括位点方面微生物数据;通过实验室处理和/或下游生物信息学方法;等);确定位点方面的倾向性分值(例如,基于用微生物组表征模块221确定的位点方面微生物组特征;通过位点方面微生物有关状况倾向性估计算法;通过包括机器学习模型、回归模型、聚类算法中至少之一的分析技术,该聚类算法基于先前学习的参数或非参数函数针对疾病倾向性评分微生物组概况,等);和基于位点方面倾向性分值、位点对位点微生物组概况的非显著的关联模式的信息、和/或其他合适的数据确定总体倾向性分值。多位点分析(例如,组合来自不同位点的补充信息以生成总体指标,等)可以提供微生物有关状况倾向性的整体测量(holistic measure),这例如可以与患者物候(phenology)整合以指导诊断和治疗决策(例如,促进治疗干预等)。然而,微生物组表征系统和/或其他合适的组件可以以任何合适的方式配置,以促进多位点分析(例如,将分析技术应用于多位点分析目的;生成多位点表征;等)。In a particular embodiment, as shown in FIG. 17 , an overall propensity score (e.g., for one or more microbial-related conditions) can be determined by one or more of the following: collecting samples from users from two or more collection sites; determining a multi-site microbial dataset (e.g., including site-wise microbial data; by laboratory processing and/or downstream bioinformatics methods; etc.); determining a site-wise propensity score (e.g., based on site-wise microbial group characteristics determined using the microbiome characterization module 221; by a site-wise microbial-related condition propensity estimation algorithm; by an analytical technique comprising at least one of a machine learning model, a regression model, a clustering algorithm that scores a microbial group profile for a disease propensity based on a previously learned parametric or non-parametric function, etc.); and determining an overall propensity score based on the site-wise propensity score, information on non-significant association patterns of site-to-site microbial group profiles, and/or other suitable data. Multi-site analysis (e.g., combining complementary information from different sites to generate an overall index, etc.) can provide a holistic measure of microbial propensity for a condition, which can be integrated with patient phenology to guide diagnostic and treatment decisions (e.g., facilitate therapeutic interventions, etc.). However, the microbiome characterization system and/or other suitable components can be configured in any suitable manner to facilitate multi-site analysis (e.g., applying an analytical technique to a multi-site analysis purpose; generating a multi-site characterization; etc.).
微生物组表征系统可优选针对多种微生物有关状况执行交叉条件分析(例如,使用一个或多个微生物组表征模块221;基于微生物组表征模块221的输出生成多条件表征,诸如多条件微生物组特征;等)。例如,微生物组表征系统可基于微生物数据、微生物组特征和/或与多种微生物有关状况相关联(例如,诊断有多种微生物有关状况、由多种微生物有关状况表征等)的用户的其他合适的微生物组特性,表征微生物有关状况之间的关系。在一特定实施例中,可以基于针对个体微生物有关状况的表征(例如,来自微生物组表征模块221的针对单个微生物有关状况的输出,等)执行交叉条件分析。交叉条件分析可以包括条件特定特征(例如,仅与单个微生物有关状况相关联,等)、多条件特征(例如,与两个以上微生物有关状况相关,等)、和/或任何其他合适类型的特征的识别。交叉条件分析可以包括诸如通过评价不同对的微生物有关状况,确定报告关联性、一致性的参数和/或描述两种以上微生物有关状况之间的关系的其他类似参数,其中具有较高参数值排名的对可以与微生物组特征的更大相似度(例如,共享)相关联。在一实施例中,交叉条件分析可以包括来自多个微生物有关状况的、关于相关联微生物组特性(例如,微生物数据、微生物组特征等)的数据的联合分析。交叉条件分析可包括分析技术的应用,分析技术包括以下任何一项或多项:多变量模型、典型关联模型、多标签人工智能方法(例如,多标签监督的、多标签无监督的、多标签半监督的机器学习或人工智能方法,等)、和/或任何其他合适的分析技术(例如,用于微生物组表征模块221在分析单个微生物有关状况和比较所得的表征中的应用,等)。然而,微生物组表征系统和/或其他合适的组件可以以任何合适的方式配置,以促进交叉条件分析(例如,将分析技术应用于交叉条件分析目的;生成交叉条件表征,等)。The microbiome characterization system may preferably perform cross-condition analysis for multiple microbiome-related conditions (e.g., using one or more microbiome characterization modules 221; generating multi-conditional characterizations based on the output of the microbiome characterization module 221, such as multi-conditional microbiome features; etc.). For example, the microbiome characterization system may characterize the relationship between microbiome-related conditions based on microbial data, microbiome features, and/or other suitable microbiome characteristics of a user associated with multiple microbiome-related conditions (e.g., diagnosed with multiple microbiome-related conditions, characterized by multiple microbiome-related conditions, etc.). In a particular embodiment, cross-condition analysis may be performed based on characterizations for individual microbiome-related conditions (e.g., outputs from the microbiome characterization module 221 for a single microbiome-related condition, etc.). The cross-condition analysis may include identification of condition-specific features (e.g., associated only with a single microbiome-related condition, etc.), multi-conditional features (e.g., associated with more than two microbiome-related conditions, etc.), and/or any other suitable type of features. Cross-condition analysis can include, for example, determining parameters for reporting association, consistency, and/or other similar parameters describing the relationship between two or more microbial-related conditions by evaluating different pairs of microbial-related conditions, wherein pairs with higher parameter value rankings can be associated with greater similarity (e.g., sharing) of microbial group features. In one embodiment, cross-condition analysis can include joint analysis of data from multiple microbial-related conditions about associated microbial group characteristics (e.g., microbial data, microbial group features, etc.). Cross-condition analysis can include the application of analysis techniques, which include any one or more of the following: multivariate models, canonical association models, multi-label artificial intelligence methods (e.g., multi-label supervised, multi-label unsupervised, multi-label semi-supervised machine learning or artificial intelligence methods, etc.), and/or any other suitable analysis techniques (e.g., for the application of microbial group characterization module 221 in analyzing single microbial-related conditions and comparing the resulting characterizations, etc.). However, the microbial group characterization system and/or other suitable components can be configured in any suitable manner to facilitate cross-condition analysis (e.g., applying analysis techniques to cross-condition analysis purposes; generating cross-condition characterizations, etc.).
微生物组表征系统220优选地包括远程计算系统(例如,用于应用微生物组表征模块221,等),但是可以附加地或可替代地包括任何合适的计算系统(例如,本地计算系统、用户设备、处理系统组件等)。然而,微生物组表征系统220可以以任何合适的方式配置。The microbiome characterization system 220 preferably includes a remote computing system (e.g., for applying the microbiome characterization module 221, etc.), but may additionally or alternatively include any suitable computing system (e.g., a local computing system, a user device, a processing system component, etc.). However, the microbiome characterization system 220 can be configured in any suitable manner.
系统200的疗法促进系统230可以起到针对一种或多种微生物有关状况促进治疗干预(例如,推广一种或多种疗法等)的作用(例如,促进用户微生物组组成和功能多样性的调节,以改进关于一种或多种微生物有关状况的用户状态,等)。疗法促进系统230可以诸如基于多位点表征、多条件表征、其他表征、和/或任何其他合适的数据,针对任何数量的微生物有关状况促进治疗干预,该任何数量的微生物有关状况与任何数量的收集位点相关联。疗法促进系统230可以包括以下任何一个或多个:通信系统(例如,将疗法建议、选择、劝阻和/或其他合适的疗法有关信息通讯给用户设备和/或护理提供者设备;使得护理提供者和关于微生物有关状况的受试者之间能够远程医疗;等)、在用户设备上可执行的应用程序(例如,针对用户指示微生物组组成和/或功能等)、医疗设备(例如,诸如用于从不同收集位点收集样品的生物采样设备、药物提供设备、手术系统等)、用户设备(例如,生物统计(biometric)传感器)和/或任何其他合适的组件。一个或多个疗法促进系统230可以是可控制的、可与微生物组表征系统220通讯的、和/或以其他方式与微生物组表征系统220相关联。例如,微生物组表征系统220可以为疗法促进系统230生成一种或多种微生物有关状况的表征,以呈现(例如,传输、通讯等)给相应的用户(例如,在接口240处等)。在另一实施例中,疗法促进系统230可以更新和/或以其他方式修改设备(例如,用户智能手机)的应用程序和/或其他软件,以推广疗法(例如,在待办事项列表应用程序中推广生活方式的改变,以改进与一种或多种微生物有关状况相关联的用户状态,等)。然而,疗法促进系统230可以以任何其他方式配置。The therapy promotion system 230 of the system 200 can function to promote therapeutic interventions (e.g., promote one or more therapies, etc.) for one or more microbial-related conditions (e.g., promote the modulation of the composition and functional diversity of the user's microbiome to improve the user's status with respect to one or more microbial-related conditions, etc.). The therapy promotion system 230 can promote therapeutic interventions for any number of microbial-related conditions, such as based on multi-site characterization, multi-condition characterization, other characterization, and/or any other suitable data, and the any number of microbial-related conditions are associated with any number of collection sites. The therapy promotion system 230 can include any one or more of the following: a communication system (e.g., communicating therapy recommendations, selections, dissuasion, and/or other suitable therapy-related information to a user device and/or a care provider device; enabling telemedicine between a care provider and a subject with respect to a microbial-related condition; etc.), an application executable on a user device (e.g., indicating microbial composition and/or function to a user, etc.), a medical device (e.g., such as a biological sampling device for collecting samples from different collection sites, a drug delivery device, a surgical system, etc.), a user device (e.g., a biometric sensor), and/or any other suitable component. One or more therapy facilitation systems 230 may be controllable, communicable with, and/or otherwise associated with the microbiome characterization system 220. For example, the microbiome characterization system 220 may generate representations of one or more microbiome-related conditions for the therapy facilitation system 230 to present (e.g., transmit, communicate, etc.) to a corresponding user (e.g., at an interface 240, etc.). In another embodiment, the therapy facilitation system 230 may update and/or otherwise modify an application and/or other software of a device (e.g., a user's smartphone) to promote a therapy (e.g., promoting lifestyle changes in a to-do list application to improve a user's status associated with one or more microbiome-related conditions, etc.). However, the therapy facilitation system 230 may be configured in any other manner.
如图9所示,系统200可以附加地或可替代地包括接口240,该接口240可以起到改进微生物组特征、微生物有关状况信息(例如,倾向性指标、疗法建议、与其他用户的比较、其他表征等)的呈现的作用。在实施例中,接口240可以呈现微生物有关状况信息,该微生物有关状况信息包括:微生物组组成(例如,分类组、相对丰度等)、功能多样性(例如,与特定功能相关联的基因相对丰度)、以及诸如相对于共享人口统计学特性的用户组(例如,吸烟者、锻炼者、采用不同饮食养生的用户、益生菌的消耗者、抗生素用户、经历特定疗法的组等)的、针对一种或多种微生物有关状况的倾向性指标。然而,接口240可以以任何合适的方式配置。As shown in FIG9 , the system 200 may additionally or alternatively include an interface 240 that may serve to improve the presentation of microbiome features, microbiome-related condition information (e.g., propensity indicators, therapy recommendations, comparisons with other users, other characterizations, etc.). In an embodiment, the interface 240 may present microbiome-related condition information, including: microbiome composition (e.g., taxonomic groups, relative abundance, etc.), functional diversity (e.g., relative abundance of genes associated with a particular function), and propensity indicators for one or more microbiome-related conditions, such as relative to a user group sharing demographic characteristics (e.g., smokers, exercisers, users who adopt different dietary regimens, consumers of probiotics, antibiotic users, groups undergoing specific therapies, etc.). However, the interface 240 may be configured in any suitable manner.
虽然系统200的组件通常被描述为不同的组件,但是它们可以以任何方式在物理和/或逻辑上整合。例如,计算系统(例如,远程计算系统,用户设备,等)可以实施微生物组表征系统220(例如,应用微生物组有关状况模型以针对用户生成微生物有关状况的表征,等)和疗法促进系统230(例如,通过呈现与微生物组组成和/或功能相关联的见解来促进治疗干预;呈现治疗建议和/或信息;在智能手机的日历应用程序中安排每日事件以通知用户采取基于表征识别的益生菌疗法,等)的部分和/或全部。然而,系统200的功能可以以任何合适的方式分布在任何合适的系统组件之中。附加地或可替代地,系统200和/或方法100可以包括与在2015年1月9日提交的14/593,424号美国专利申请中描述的组件和/或功能类似的任何合适的组件和/或功能,该专利申请的全部内容通过该引用合并于此。然而,系统200的组件可以以任何合适的方式配置。Although the components of system 200 are generally described as distinct components, they may be physically and/or logically integrated in any manner. For example, a computing system (e.g., a remote computing system, a user device, etc.) may implement part and/or all of microbiome characterization system 220 (e.g., applying a microbiome-related condition model to generate a characterization of a microbiome-related condition for a user, etc.) and therapy promotion system 230 (e.g., promoting therapeutic intervention by presenting insights associated with microbiome composition and/or function; presenting therapeutic recommendations and/or information; scheduling daily events in a smartphone calendar application to notify the user to take a probiotic therapy based on characterization identification, etc.). However, the functionality of system 200 may be distributed among any suitable system components in any suitable manner. Additionally or alternatively, system 200 and/or method 100 may include any suitable components and/or functionality similar to those described in U.S. Patent Application No. 14/593,424, filed on January 9, 2015, the entire contents of which are incorporated herein by reference. However, the components of system 200 may be configured in any suitable manner.
4.1生成微生物数据集4.1 Generating microbial datasets
框S110可以包括确定与受试者集合相关联的微生物数据集(例如,微生物序列数据集、诸如基于微生物序列数据集的微生物组组成多样性数据集、诸如基于微生物序列数据集的微生物组功能多样性数据集等)S110。框S110可以起到处理生物样品(例如,与受试者群体、受试者的亚群体、共享人口统计学特性和/或其他合适特性的受试者亚组相关联的生物样品聚合集合)的作用,以便确定与相应的微生物组相关联的组成、功能、药物基因组学和/或其他合适的方面,诸如关于一种或多种微生物有关状况。组成和/或功能方面可包括在微生物水平上(和/或其他合适的粒度(granularity))的一个或多个方面,包括与微生物跨不同组的界(kingdom)、门、纲、目、科、属、种、亚种、品系和/或任何其他合适的种下(infraspecies)分类单元(taxon)(例如,按各组的总丰度、各组的相对丰度、所代表的组的总数来测量的,等)中的分布有关的参数。组成和/或功能方面也可以依据操作分类单位(operational taxonomic units,OTUs)表示。组成和/或功能方面可以附加地或可替代地包括在遗传水平上的组成方面(例如,由多位点序列分型确定的区域,16S序列,18S序列,ITS序列,其他遗传标志物,其他系统发育标志物,等)。组成和功能方面可以包括与特定功能(例如,酶活性、转运功能、免疫活性等)相关联的基因的存在或不存在或量。因此,框S110的输出可以用于促进用于框S130的表征过程和/或方法100的其他合适部分(例如,其中框S110可导致微生物组组成数据集、微生物组功能数据集和/或从中可提取微生物组特征的其他合适的微生物数据集的输出,等)的微生物组特征(例如,可用于识别微生物组特征的微生物序列数据级的生成,等)的确定,其中特征可以是基于微生物的(例如,细菌属的存在)、基于遗传的(例如,基于特定遗传区域和/或序列的代表)、基于功能的(例如,特定的催化活性的存在)和/或任何其他合适的微生物组特征。Block S110 may include determining a microbial dataset associated with a subject set (e.g., a microbial sequence dataset, a microbial composition diversity dataset such as based on a microbial sequence dataset, a microbial functional diversity dataset such as based on a microbial sequence dataset, etc.) S110. Block S110 may function to process biological samples (e.g., an aggregated set of biological samples associated with a subject population, a subpopulation of subjects, a subgroup of subjects sharing demographic characteristics and/or other suitable characteristics) to determine composition, function, pharmacogenomics, and/or other suitable aspects associated with a corresponding microbial group, such as regarding one or more microbial related conditions. The composition and/or functional aspects may include one or more aspects at the microbial level (and/or other suitable granularity), including parameters related to the distribution of microorganisms across different groups of kingdoms, phyla, classes, orders, families, genera, species, subspecies, strains, and/or any other suitable infraspecies taxon (e.g., measured by the total abundance of each group, the relative abundance of each group, the total number of groups represented, etc.). Compositional and/or functional aspects may also be expressed in terms of operational taxonomic units (OTUs). Compositional and/or functional aspects may additionally or alternatively include compositional aspects at the genetic level (e.g., regions determined by multilocus sequence typing, 16S sequences, 18S sequences, ITS sequences, other genetic markers, other phylogenetic markers, etc.). Compositional and functional aspects may include the presence or absence or amount of genes associated with a particular function (e.g., enzymatic activity, transport function, immune activity, etc.). Thus, the output of block S110 can be used to facilitate determination of microbiome features (e.g., generation of microbial sequence data that can be used to identify microbiome features, etc.) for the characterization process of block S130 and/or other suitable portions of method 100 (e.g., where block S110 can result in output of a microbiome composition dataset, a microbiome function dataset, and/or other suitable microbial dataset from which microbiome features can be extracted, etc.), where the features can be microbial-based (e.g., the presence of a bacterial genus), genetic-based (e.g., based on representation of particular genetic regions and/or sequences), functional-based (e.g., the presence of a particular catalytic activity), and/or any other suitable microbiome feature.
在一个变型中,框S110可以包括基于关于基因家族的、衍生自细菌和/或古生菌的系统发育标志物(例如,用于生成微生物数据集,等)的评估和/或处理,该基因家族与以下一项或多项相关联:核糖体蛋白S2、核糖体蛋白S3、核糖体蛋白S5、核糖体蛋白S7、核糖体蛋白S8、核糖体蛋白S9、核糖体蛋白S10、核糖体蛋白S11、核糖体蛋白S12/S23、核糖体蛋白S13、核糖体蛋白S15P/S13e、核糖体蛋白S17、核糖体蛋白S19、核糖体蛋白L1、核糖体蛋白L2、核糖体蛋白L3、核糖体蛋白L4/L1e、核糖体蛋白L5、核糖体蛋白L6、核糖体蛋白L10、核糖体蛋白L11、核糖体蛋白L14b/L23e、核糖体蛋白L15、核糖体蛋白L16/L10E、核糖体蛋白L18P/L5E、核糖体蛋白L22、核糖体蛋白L24、核糖体蛋白L25/L23、核糖体蛋白L29、翻译延伸因子EF-2、翻译起始因子IF-2、金属内肽酶、ffh信号识别颗粒蛋白,苯丙氨酰-tRNA合成酶β亚基、苯丙氨酰-tRNA合成酶α亚基、tRNA假尿苷合酶B、胆色素原脱氨酶、核糖体蛋白L13、磷酸核糖基甲酰甘氨脒环连接酶(phosphoribosylformylglycinamidine cyclo-ligase)和核糖核酸酶HII。附加地或可替代地,标志物可以包括:靶序列(例如,与微生物分类组相关联的序列;与功能方面相关联的序列;与微生物有关状况关联的序列;指示用户对不同疗法的反应性的序列;跨群体和/或任何其他合适的受试者集合的不变量的序列,例如以使用共享引物序列的引物类型促进多重扩增;保守序列;包括突变、多态性的序列;核苷酸序列;氨基酸序列;等)、蛋白质(例如,血清蛋白、抗体等)、肽、碳水化合物、脂质、其他核酸、全细胞、代谢物、天然产物、遗传易感性生物标志物物、诊断性生物标志物、预后性生物标志物、预测性生物标志物、其他分子生物标志物、基因表达标志物、成像生物标志物和/或其他合适的标志物。然而,标志物可以包括与微生物组组成、微生物组功能和/或微生物有关状况相关联的任何其他合适的标志物。In one variation, block S110 can include an evaluation and/or processing based on phylogenetic markers derived from bacteria and/or archaea (e.g., for generating a microbial dataset, etc.) regarding a gene family associated with one or more of the following: ribosomal protein S2, ribosomal protein S3, ribosomal protein S5, ribosomal protein S7, ribosomal protein S8, ribosomal protein S9, ribosomal protein S10, ribosomal protein S11, ribosomal protein S12/S23, ribosomal protein S13, ribosomal protein S15P/S13e, ribosomal protein S17, ribosomal protein S19, ribosomal protein L1, ribosomal protein L2, ribosomal protein L3, ribosomal protein L4/L5, ribosomal protein L6, ribosomal protein L7, ribosomal protein L8, ribosomal protein L9, ribosomal protein S10, ribosomal protein S11, ribosomal protein S12/S23, ribosomal protein S13, ribosomal protein S15P/S13e, ribosomal protein S17, ribosomal protein S19, ribosomal protein L1, ribosomal protein L2, ribosomal protein L3, ribosomal protein L4/L5e, ribosomal protein L6 6. Ribosomal protein L10, ribosomal protein L11, ribosomal protein L14b/L23e, ribosomal protein L15, ribosomal protein L16/L10E, ribosomal protein L18P/L5E, ribosomal protein L22, ribosomal protein L24, ribosomal protein L25/L23, ribosomal protein L29, translation elongation factor EF-2, translation initiation factor IF-2, metalloendopeptidase, ffh signal recognition granule protein, phenylalanyl-tRNA synthetase β subunit, phenylalanyl-tRNA synthetase α subunit, tRNA pseudouridine synthase B, porphobilinogen deaminase, ribosomal protein L13, phosphoribosylformylglycinamidine cyclo-ligase and ribonuclease HII. Additionally or alternatively, markers may include: target sequences (e.g., sequences associated with microbial taxonomic groups; sequences associated with functional aspects; sequences associated with microbial-related conditions; sequences indicating user responsiveness to different therapies; sequences that are invariant across populations and/or any other suitable subject collections, such as to facilitate multiplex amplification using primer types that share primer sequences; conserved sequences; sequences including mutations, polymorphisms; nucleotide sequences; amino acid sequences; etc.), proteins (e.g., serum proteins, antibodies, etc.), peptides, carbohydrates, lipids, other nucleic acids, whole cells, metabolites, natural products, genetic susceptibility biomarkers, diagnostic biomarkers, prognostic biomarkers, predictive biomarkers, other molecular biomarkers, gene expression markers, imaging biomarkers, and/or other suitable markers. However, markers may include any other suitable markers associated with microbiome composition, microbiome function, and/or microbial-related conditions.
因此,针对各生物样品聚合集合的表征微生物组组成和/或功能方面,优选地包括样品处理技术(例如,湿实验室技术;如图5所示)的组合,该样品处理技术包括但不限于扩增子测序(例如16S、18S、ITS)、唯一分子标识符(Unique Molecular Identifier,UMI)、3步聚合酶链反应(3step PCR)、聚类规则间隔短回文重复序列(clustered regularlyinterspaced short palindromic repeatsequences,Crispr)、宏基因组学方法、元转录组学(metatranscriptomics)、随机引物的使用和计算技术(例如,利用生物信息学工具),以定量地和/或定性地表征与来自受试者或受试者群体的各生物样品相关联的微生物组和功能方面。Therefore, characterizing the microbiome composition and/or functional aspects of each biological sample aggregation set preferably includes a combination of sample processing techniques (e.g., wet lab techniques; as shown in Figure 5), which sample processing techniques include but are not limited to amplicon sequencing (e.g., 16S, 18S, ITS), unique molecular identifiers (Unique Molecular Identifier, UMI), 3-step polymerase chain reaction (3step PCR), clustered regularly interspaced short palindromic repeat sequences (crispr), metagenomics methods, metatranscriptomics, the use of random primers and computational techniques (e.g., using bioinformatics tools) to quantitatively and/or qualitatively characterize the microbiome and functional aspects associated with each biological sample from a subject or a population of subjects.
在变型中,框S110中的样品处理可以包括以下任何一项或多项:裂解生物样品、破坏生物样品的细胞中的膜、从生物样品中分离不期望的元素(例如,RNA、蛋白质)、纯化生物样品中的核酸(例如,DNA)、从生物样品中扩增核酸、进一步纯化生物样品的扩增的核酸、以及对生物样品的扩增的核酸进行测序。在一实施例中,框S110可以包括:从用户集合收集生物样品(例如,由用户使用包括样品容器的采样试剂盒收集的生物样品,等),其中生物样品包括与微生物有关状况相关联的微生物核酸(例如,包括与微生物有关状况关联的靶序列的微生物核酸,等)。在另一实施例中,框S110可以包括向用户集合提供采样试剂盒集合,该采样试剂盒集合中的各采样试剂盒包括样品容器(例如,包括例如裂解试剂的预处理试剂;等),该样品容器可操作以从用户集合中的一个用户接收生物样品。In a variation, the sample processing in block S110 may include any one or more of: lysing a biological sample, disrupting membranes in cells of the biological sample, separating undesirable elements (e.g., RNA, proteins) from the biological sample, purifying nucleic acids (e.g., DNA) from the biological sample, amplifying nucleic acids from the biological sample, further purifying the amplified nucleic acids of the biological sample, and sequencing the amplified nucleic acids of the biological sample. In one embodiment, block S110 may include: collecting biological samples from a user set (e.g., biological samples collected by a user using a sampling kit including a sample container, etc.), wherein the biological sample includes a microbial nucleic acid associated with a microbial-related condition (e.g., a microbial nucleic acid including a target sequence associated with a microbial-related condition, etc.). In another embodiment, block S110 may include providing a sampling kit set to the user set, each sampling kit in the sampling kit set including a sample container (e.g., including a pretreatment reagent such as a lysis reagent; etc.), which is operable to receive a biological sample from a user in the user set.
在变型中,裂解生物样品和/或破坏生物样品的细胞中的膜优选地包括物理方法(例如,珠打、氮解压缩、均质化、超声处理),其省略了在基于测序表示某些细菌组中产生偏差的某些试剂。附加地或可替代地,框S110中的裂解或破坏可以涉及化学方法(例如,使用清洁剂、使用溶剂、使用表面活性剂等)。附加地或可替代地,框S110中的裂解或破坏可以涉及生物学方法。在变型中,分离不期望的元素可以包括使用核糖核酸酶(RNase)去除RNA和/或使用蛋白酶去除蛋白质。在变型中,纯化核酸可包括以下一项或多项:(例如,使用基于醇类的沉淀法)从生物样品中沉淀核酸、基于液-液的纯化技术(例如,苯酚-氯仿提取)、基于色谱法的纯化技术(例如,柱吸附)、涉及结合部分结合颗粒(moiety-bound particles)(例如,磁珠、浮力珠、具有尺寸分布的珠子、超声响应珠等)的使用的纯化技术,该部分结合颗粒被配置为结合核酸并配置为在洗脱环境(例如,具有洗脱溶液、提供pH值变化、提供温度变化等)的存在下释放核酸、以及任何其他合适的纯化技术。In a variation, the membranes in the cells of the lysing biological sample and/or the destruction of the biological sample preferably include physical methods (e.g., bead beating, nitrogen decompression, homogenization, ultrasonic treatment), which omits certain reagents that produce biases in the sequencing-based representation of certain bacterial groups. Additionally or alternatively, the lysis or destruction in frame S110 can involve chemical methods (e.g., using detergents, using solvents, using surfactants, etc.). Additionally or alternatively, the lysis or destruction in frame S110 can involve biological methods. In a variation, separating undesirable elements can include removing RNA using ribonucleases (RNases) and/or removing proteins using proteases. In variations, purifying nucleic acids may include one or more of the following: precipitation of nucleic acids from a biological sample (e.g., using an alcohol-based precipitation method), liquid-liquid based purification techniques (e.g., phenol-chloroform extraction), chromatography-based purification techniques (e.g., column adsorption), purification techniques involving the use of moiety-bound particles (e.g., magnetic beads, buoyant beads, beads with a size distribution, ultrasound-responsive beads, etc.), which moiety-bound particles are configured to bind nucleic acids and are configured to release nucleic acids in the presence of an elution environment (e.g., having an elution solution, providing a pH change, providing a temperature change, etc.), and any other suitable purification technique.
在变型中,纯化的核酸的扩增可包括以下一项或多项:基于聚合酶链反应(polymerase chain reaction,PCR)的技术(例如,固相PCR、反转录-PCR(RT-PCR)、定量PCR(qPCR)、多重PCR、降落式(touchdown)PCR、纳米(nano)PCR、巢式(nested)PCR、热启动PCR等)、解旋酶依赖性扩增(helicase-dependent amplification,HDA)、环介导等温扩增(loop mediated isothermal amplification,LAMP)、自我维持序列复制(self-sustainedsequence replication,3SR)、基于核酸序列的扩增(nucleic acid sequence basedamplification,NASBA)、链置换扩增(strand dsplacement amplification,SDA)、滚环扩增(rolling circle amplification,RCA)、连接酶链反应(ligase chain reaction,LCR)和任何其他合适的扩增技术。在纯化的核酸的扩增中,所用的引物优选选择以防止或最小化扩增偏差,以及配置为扩增(例如,16S区域的、18S区域的、ITS区域的等)核酸区域/序列,该核算区域或序列对诊断、对制剂(例如,对益生菌制剂)和/或对任何其他合适的目,在分类学上、在系统发育上是提供有用信息的。因此,配置为避免扩增偏差的通用引物(例如,用于16S RNA的F27-R338引物集,用于16S RNA的F515-R806引物集,等)可以在扩增中使用。附加地或可替代地,包括特定于生物样品、用户、微生物有关状况、分类群(taxa)、靶序列和/或任何其他合适成分的合并的条形码序列和/或UMI,其可促进测序后(post-squencing)识别过程(例如,用于将序列读数(sequence reads)映射到微生物组组成和/或微生物组功能方面;等)。框S110的变型中使用的引物可以附加地或可替代地包括衔接子区域,该衔接子区域配置为与涉及互补衔接子(complementary adaptor)的测序技术(例如,宜曼达(Illumina)测序)配合。附加地或可替代地,框S110可以实施配置为(例如,使用新纪元(Nextera)试剂盒)促进处理的任何其他步骤。在一特定实施例中,执行扩增和/或样品处理操作可以以多重方式进行(例如,对于单个生物样品、对于跨多个用户的多个生物样品等)。在另一特定实施例中,执行扩增可包括标准化步骤以平衡库并检测独立于起始材料量中的所有扩增子,例如3步PCR、基于珠子(bead)的标准化和/或其他合适的技术。In a variation, amplification of the purified nucleic acid may include one or more of the following: polymerase chain reaction (PCR)-based techniques (e.g., solid phase PCR, reverse transcription-PCR (RT-PCR), quantitative PCR (qPCR), multiplex PCR, touchdown PCR, nano PCR, nested PCR, hot start PCR, etc.), helicase-dependent amplification (HDA), loop mediated isothermal amplification (LAMP), self-sustained sequence replication (3SR), nucleic acid sequence based amplification (NASBA), strand displacement amplification (SDA), rolling circle amplification (RCA), ligase chain reaction (LCR), and any other suitable amplification technique. In the amplification of the purified nucleic acid, the primers used are preferably selected to prevent or minimize amplification bias, and are configured to amplify a nucleic acid region/sequence (e.g., 16S region, 18S region, ITS region, etc.), which is useful information for diagnosis, preparation (e.g., probiotic preparation) and/or any other suitable purpose, taxonomically and phylogenetically. Therefore, universal primers configured to avoid amplification bias (e.g., F27-R338 primer set for 16S RNA, F515-R806 primer set for 16S RNA, etc.) can be used in amplification. Additionally or alternatively, a combined barcode sequence and/or UMI specific to a biological sample, a user, a microbial-related condition, a taxa, a target sequence, and/or any other suitable component is included, which can facilitate a post-sequencing identification process (e.g., for mapping sequence reads to microbiome composition and/or microbiome functional aspects; etc.). The primers used in the variant of block S110 may additionally or alternatively include an adapter region configured to cooperate with a sequencing technology involving a complementary adapter (e.g., Illumina sequencing). Additionally or alternatively, block S110 may implement any other steps configured to facilitate processing (e.g., using a Nextera kit). In a particular embodiment, performing amplification and/or sample processing operations may be performed in a multiplexed manner (e.g., for a single biological sample, for multiple biological samples across multiple users, etc.). In another particular embodiment, performing amplification may include a standardization step to balance the library and detect all amplicons independent of the amount of starting material, such as 3-step PCR, bead-based standardization, and/or other suitable techniques.
在变型中,纯化的核酸的测序可以包括涉及靶向扩增子测序、元转录组测序和/或宏基因组测序的方法,实施技术包括以下一项或多项:合成测序技术(例如,Illumina测序)、毛细管测序技术(例如,桑格测序)、焦磷酸测序技术和纳米孔测序技术(例如,使用牛津纳米孔技术)。In variations, sequencing of purified nucleic acids can include methods involving targeted amplicon sequencing, metatranscriptome sequencing, and/or metagenomic sequencing, implemented using one or more of the following techniques: synthetic sequencing technology (e.g., Illumina sequencing), capillary sequencing technology (e.g., Sanger sequencing), pyrosequencing technology, and nanopore sequencing technology (e.g., using Oxford Nanopore technology).
在一特定实施例中,来自生物样品集合的生物样品的核酸的扩增和测序包括:涉及使用寡核苷酸衔接子桥式扩增(bridge amplification)底物上的生物样品的DNA片段的固相PCR,其中扩增涉及引物,该引物具有正向索引序列(forward index sequence)(例如,对应于NextSeq/HiSeq平台的Illumina正向索引)、正向条形码序列、转座酶序列(例如,对应于MiSeq/NextSeq/HiSeq平台的转座酶结合位点)、接头(例如,配置为减少均一性并改善序列结果的零个、一个或两个碱基片段)、另外的随机碱基、UMI、用于靶向特定靶标区域(例如,16S区域、18S区域、ITS区域)的序列、反向索引序列(例如,对应于MiSeq/HiSeq平台的Illumina反向索引)和反向条形码序列。在特定实施例中,测序可以包括使用合成测序技术的Illumina测序(例如,使用HiSeq平台,使用MiSeq平台,使用NextSeq平台,等)。在另一特定实施例中,方法100可以包括:识别与一种或多种遗传靶标兼容的一种或多种类引物类型,该一种或多种遗传靶标与一种或多种微生物有关状况(例如,人类行为状况、疾病有关状况等)相关联;诸如通过片段化微生物核酸进行和/或基于与遗传靶标兼容的一种或多种识别的引物类型使用片段化的微生物核酸执行多重扩增,来基于一种或多种引物类型(例如,以及包括在所收集的生物样品中的微生物核酸,等)针对一个或多个用户(例如,受试者集合)生成微生物数据集(例如,微生物序列数据集等),所述遗传靶标与人类行为状况相关联;和/或基于衍生自微生物数据集的微生物有关表征推广(例如,提供)针对用户状况的疗法(例如,能够选择性调节关于期望的分类单元(taxon)的群体尺寸和期望的微生物组功能的至少之一的用户的微生物组,等)。In a specific embodiment, amplification and sequencing of nucleic acids from biological samples of a biological sample collection includes solid-phase PCR involving DNA fragments of the biological sample on a substrate using oligonucleotide adapters for bridge amplification, wherein the amplification involves primers having a forward index sequence (e.g., an Illumina forward index corresponding to a NextSeq/HiSeq platform), a forward barcode sequence, a transposase sequence (e.g., a transposase binding site corresponding to a MiSeq/NextSeq/HiSeq platform), an adapter (e.g., a zero, one, or two base fragment configured to reduce uniformity and improve sequence results), additional random bases, a UMI, a sequence for targeting a specific target region (e.g., a 16S region, a 18S region, an ITS region), a reverse index sequence (e.g., an Illumina reverse index corresponding to a MiSeq/HiSeq platform), and a reverse barcode sequence. In a particular embodiment, sequencing may include Illumina sequencing using synthetic sequencing technology (e.g., using a HiSeq platform, using a MiSeq platform, using a NextSeq platform, etc.). In another particular embodiment, method 100 may include: identifying one or more class primer types compatible with one or more genetic targets, the one or more genetic targets being associated with one or more microbial-related conditions (e.g., human behavioral conditions, disease-related conditions, etc.); generating a microbial dataset (e.g., a microbial sequence dataset, etc.) for one or more users (e.g., a subject set) based on one or more primer types (e.g., and microbial nucleic acids included in the collected biological samples, etc.), such as by fragmenting microbial nucleic acids and/or performing multiplex amplification using fragmented microbial nucleic acids based on one or more identified primer types compatible with the genetic targets, the genetic targets being associated with human behavioral conditions; and/or promoting (e.g., providing) a therapy for a user's condition based on a microbial-related characterization derived from the microbial dataset (e.g., a user's microbiome that can selectively adjust at least one of a population size of a desired taxon and a desired microbiome function, etc.).
在变型中,框S110、和/或方法100的其他合适部分中使用的引物(例如,对应于引物序列的引物类型;等)可以包括与蛋白质基因相关联的引物(例如,针对跨多个分类群的保守蛋白基因序列编码,诸如以能够对多个靶标和/或分类群多重扩增;等)。引物可以附加地或可替代地与以下相关联:微生物有关状况(例如,与包括微生物序列生物标志物的遗传靶标兼容的引物,该微生物序列生物标志物用于与诸如人类行为状况和/或疾病有关状况的微生物有关状况关联的微生物;等)、微生物组组成特征(例如,与对应于微生物组组成特征的遗传靶标兼容的识别的引物,该微生物组组成特征与分类群组相关联,该分类群组与微生物有关状况关联;自其衍生相对丰度特征的遗传序列,等)、功能多样性特征、补充特征和/或其他合适的功能和/或数据。引物(和/或本文中描述的其他合适的分子、标志物和/或生物材料)可具有任何合适的尺寸(例如,序列长度、碱基对数量、保守序列长度、可变区长度等)。附加地或可替代地,可以在样品处理中使用任何合适数量的引物,以用于执行表征(例如,微生物有关表征;等)、改进样品处理(例如,通过减少扩增偏差,等)、和/或用于任何合适的目的。引物可以与任何合适数量的靶标、序列、分类群、状况和/或其他合适方面相关联。可以通过框S110中描述的过程、和/或方法100的任何其他合适的部分,选择在框S110(例如,基于在生成分类数据库中使用的参数的引物选择)、和/或方法100的其他合适部分中使用的引物。在一实施例中,框S110可以包括:识别与微生物有关状况相关联的微生物核酸序列的引物类型(例如,用于可操作以扩增与微生物有关状况关联的微生物核酸序列的引物的引物类型;等);和基于引物类型和微生物核酸生成微生物序列数据集(例如,使用用于扩增微生物核酸的引物类型的引物;和测序扩增的核酸以生成微生物序列数据集;等)。在一特定实施例中,框S110可以包括:片段化微生物核酸片段;和基于片段化的微生物核酸和与微生物有关状况相关联的所识别的引物类型、用片段化的微生物核酸执行多重扩增。附加地或可替代地,引物(和/或与引物相关联的过程)可以包括和/或类似于2015年10月21日提交的14/919,614号美国专利申请中描述的引物(和/或与引物相关的过程),该专利申请的全部内容通过该引用合并于此。然而,引物的识别和/或使用可以以任何合适的方式配置。In a variation, the primers used in block S110, and/or other suitable portions of method 100 (e.g., primer types corresponding to primer sequences; etc.) may include primers associated with protein genes (e.g., for conserved protein gene sequences encoding across multiple taxa, such as to enable multiplex amplification of multiple targets and/or taxa; etc.). Primers may additionally or alternatively be associated with: microbial-associated conditions (e.g., primers compatible with genetic targets including microbial sequence biomarkers for microbes associated with microbial-associated conditions such as human behavioral conditions and/or disease-associated conditions; etc.), microbiome composition features (e.g., primers compatible with identified genetic targets corresponding to microbiome composition features, the microbiome composition features associated with taxonomic groups, the taxonomic groups associated with microbial-associated conditions; genetic sequences from which relative abundance features are derived, etc.), functional diversity features, supplemental features, and/or other suitable functions and/or data. Primers (and/or other suitable molecules, markers, and/or biological materials described herein) may have any suitable size (e.g., sequence length, number of base pairs, conserved sequence length, variable region length, etc.). Additionally or alternatively, any suitable number of primers may be used in sample processing for performing characterization (e.g., microbial-related characterization; etc.), improving sample processing (e.g., by reducing amplification bias, etc.), and/or for any suitable purpose. Primers may be associated with any suitable number of targets, sequences, taxa, conditions, and/or other suitable aspects. Primers used in box S110 (e.g., primer selection based on parameters used in generating a classification database), and/or other suitable parts of method 100 may be selected by the process described in box S110, and/or any other suitable part of method 100. In one embodiment, block S110 may include: identifying a primer type of a microbial nucleic acid sequence associated with a microbial-associated condition (e.g., a primer type for a primer operable to amplify a microbial nucleic acid sequence associated with a microbial-associated condition; etc.); and generating a microbial sequence dataset based on the primer type and the microbial nucleic acid (e.g., using primers of the primer type for amplifying the microbial nucleic acid; and sequencing the amplified nucleic acid to generate a microbial sequence dataset; etc.). In a specific embodiment, block S110 may include: fragmenting microbial nucleic acid fragments; and performing multiple amplification with the fragmented microbial nucleic acid based on the fragmented microbial nucleic acid and the identified primer type associated with the microbial-associated condition. Additionally or alternatively, the primers (and/or processes associated with the primers) may include and/or be similar to the primers (and/or processes associated with the primers) described in U.S. Patent Application No. 14/919,614 filed on October 21, 2015, the entire contents of which are incorporated herein by reference. However, the identification and/or use of primers may be configured in any suitable manner.
样品处理的某些变型可以包括在测序前进一步纯化扩增的核酸(例如,PCR产物),其起到去除多余的扩增元素(例如,引物、脱氧核糖核苷三磷酸(dNTP)、酶、盐等)的功能。在实施例中,可以使用以下任何一种或多种来促进额外的纯化:纯化试剂盒、缓冲液、醇、pH值指示剂、离液盐、核酸结合过滤器、离心和/或任何其他合适的纯化技术。Certain variations of sample processing may include further purification of the amplified nucleic acid (e.g., PCR product) prior to sequencing, which functions to remove excess amplification elements (e.g., primers, deoxyribonucleoside triphosphates (dNTPs), enzymes, salts, etc.) In embodiments, any one or more of the following may be used to facilitate additional purification: purification kits, buffers, alcohols, pH indicators, chaotropic salts, nucleic acid binding filters, centrifugation, and/or any other suitable purification technique.
在变型中,框S110中的计算处理可以包括以下任何一项或多项:微生物组衍生序列的识别(例如,与受试者序列和污染物相对)、微生物组衍生序列的比对和映射(例如,使用单端比对、无缺口(ungapped)比对、缺口比对、配对中的一项或多项的片段化序列的比对)、和生成与同生物样品相关联的微生物组的组成和/或功能方面相关联(例如,从其衍生)的特征。In variations, the computational processing in box S110 can include any one or more of the following: identification of microbiome-derived sequences (e.g., as opposed to subject sequences and contaminants), alignment and mapping of microbiome-derived sequences (e.g., alignment of fragmented sequences using one or more of single-end alignment, ungapped alignment, gapped alignment, pairwise alignment), and generation of features associated with (e.g., derived from) compositional and/or functional aspects of a microbiome associated with a biological sample.
微生物组衍生序列的识别可以包括将来自样品处理的序列数据映射到受试者参考基因组(例如,由基因组参考联盟(Genome Reference Consortium)提供),以便去除受试者基因组衍生序列。然后,在将序列数据映射到受试者参考基因组之后,剩余的未识别序列可以基于序列相似性和/或基于参考的方法(例如,使用VAMPS、使用MG-RAST、使用QIIME数据库)进一步聚类到可操作分类单元(operational taxonomic unit,OTU)中,使用比对算法(例如,基本局部比对搜索工具(Basic Local Alignment Search Tool),现场可编程门阵列(field programmable gate array,FPGA)加速比对工具、使用BWA的BWT索引、使用SOAP的BWT索引、使用Bowtie的BWT索引等)进行比对(例如,使用基因散列算法、使用内德勒曼-文施算法(Needleman-Wunsch algorithm)、使用史密斯-沃德曼算法(Smith-Watermanalgorithm))、并映射到参考细菌基因组(例如,由国家生物技术信息中心提供)。未识别序列的映射可以附加地或可替代地包括对参考古细菌基因组、病毒基因组和/或真核生物基因组的映射。此外,可以关于现有数据库和/或关于定制生成的数据库执行分类单元的映射。Identification of microbiome-derived sequences can include mapping sequence data from sample processing to a subject reference genome (eg, provided by the Genome Reference Consortium) in order to remove subject genome-derived sequences. Then, after mapping the sequence data to the subject reference genome, the remaining unidentified sequences can be further clustered into operational taxonomic units (OTUs) based on sequence similarity and/or reference-based methods (e.g., using VAMPS, using MG-RAST, using the QIIME database), aligned using an alignment algorithm (e.g., Basic Local Alignment Search Tool, field programmable gate array (FPGA) accelerated alignment tool, BWT index using BWA, BWT index using SOAP, BWT index using Bowtie, etc.) (e.g., using a gene hashing algorithm, using a Needleman-Wunsch algorithm, using a Smith-Waterman algorithm), and mapped to a reference bacterial genome (e.g., provided by the National Center for Biotechnology Information). The mapping of unidentified sequences can additionally or alternatively include mapping to reference archaeal genomes, viral genomes, and/or eukaryotic genomes. Furthermore, mapping of taxa may be performed with respect to an existing database and/or with respect to a custom generated database.
一经识别了与生物样品相关联的微生物组的微生物的代表性组,就可以执行生成与微生物组的组成和功能方面相关联(例如,从其衍生)的特征,该微生物组与生物样品相关。在一变型中,生成特征可以包括基于多位点序列分型(multilocus sequence typing,MSLT)生成特征,以便识别对方法100后续框中的表征有用的标志物。附加地或可替代地,所生成的特征可以包括生成描述某些微生物分类组的存在与否、和/或所展示微生物分类组之间的比例的特征。附加地或可替代地,生成特征可以包括生成描述以下一项或多项的特征:表示的分类组的数量、表示的分类组的网络、不同分类组的表示中的关联性、不同分类组之间的相互作用、由不同分类组产生的产物、由不同分类组产生的产物之间的相互作用、死亡微生物和活微生物之间的比例(例如,针对不同的表示的分类组,基于RNA分析)、系统发育距离(例如,依据康托洛维奇-鲁宾斯坦(Kantorovich-Rubinstein)距离、沃瑟斯坦(Wasserstein)距离等)、任何其他合适的分类组有关特征、任何其他合适的遗传或功能方面。Once a representative group of microorganisms of a microbial group associated with a biological sample has been identified, it is possible to perform the generation of features associated with (e.g., derived from) the composition and functional aspects of the microbial group, which is associated with the biological sample. In a variation, generating features may include generating features based on multilocus sequence typing (MSLT) to identify markers useful for characterization in subsequent frames of method 100. Additionally or alternatively, the generated features may include generating features describing the presence or absence of certain microbial taxonomic groups and/or the ratios between the displayed microbial taxonomic groups. Additionally or alternatively, generating features may include generating features that describe one or more of the following: the number of taxonomic groups represented, the network of taxonomic groups represented, the associations in the representation of different taxonomic groups, the interactions between different taxonomic groups, the products produced by different taxonomic groups, the interactions between products produced by different taxonomic groups, the ratio between dead and live microorganisms (e.g., for different taxonomic groups represented, based on RNA analysis), phylogenetic distances (e.g., based on Kantorovich-Rubinstein distance, Wasserstein distance, etc.), any other suitable taxonomic group-related features, any other suitable genetic or functional aspects.
附加地或可替代地,生成特征可以包括生成描述不同微生物群的相对丰度的特征,例如使用sparCC方法、使用基因组相对丰度和平均尺寸(Genome Relative Abundanceand Average size,GAAS)方法和/或使用利用混合模型理论的基因组相对丰度(GenomeRelative Abundance using Mixture Model theory,GRAMMy)方法,该利用混合模型理论的基因组相对丰度方法使用序列相似性数据来执行一个或多个微生物群的相对丰度的最大可能性估计。附加地或可替代地,生成特征可以包括生成如衍生自丰度指标的分类变化的统计测量。附加地或可替代地,生成特征可以包括生成与相对丰度因子(例如,关于影响其他分类单元丰度的分类单元丰度变化)相关联(例如,从…衍生)的特征。附加地或可替代地,生成特征可以包括隔离和/或组合地生成描述一个或多个分类组的存在的定性特征。附加地或可替代地,生成特征可以包括与遗传标志物(例如,代表性的16S、18S和/或ITS序列)有关的特征的生成,该遗传标志物表征与生物样品相关联的微生物组的微生物。附加地或可替代地,生成特征可以包括生成与特定基因和/或具有特定基因的生物体的功能关联有关的特征。附加地或可替代地,生成特征可以包括生成与分类单元和/或归因于分类单元的产物的致病性有关的特征。然而,框S120可以包括衍生自生物样品的核酸的测序和映射的任何其他合适的特征的生成。例如,特征可以是组合的(例如,涉及对、三个一组)、关联的(例如,与不同特征之间的关联性有关)和/或与特征的变化(例如,时间变化、跨样品位点的变化等、空间变化等)有关。然而,处理生物样品、生成微生物数据集和/或与框S110相关联的其他方面可以以任何合适的方式执行。Additionally or alternatively, generating features may include generating features describing the relative abundance of different microbial groups, such as using sparCC methods, using genome relative abundance and average size (Genome Relative Abundance and Average size, GAAS) methods and/or using genome relative abundance (Genome Relative Abundance using Mixture Model theory, GRAMMy) methods using mixed model theory, which uses sequence similarity data to perform the maximum likelihood estimation of the relative abundance of one or more microbial groups. Additionally or alternatively, generating features may include generating statistical measurements of classification changes such as derived from abundance indicators. Additionally or alternatively, generating features may include generating features associated with (e.g., derived from) relative abundance factors (e.g., changes in taxonomic abundance affecting other taxonomic units). Additionally or alternatively, generating features may include isolating and/or combining to generate qualitative features describing the presence of one or more taxonomic groups. Additionally or alternatively, generating features may include the generation of features related to genetic markers (e.g., representative 16S, 18S and/or ITS sequences) that characterize the microorganisms of the microbial group associated with the biological sample. Additionally or alternatively, generating features may include generating features related to the functional association of specific genes and/or organisms with specific genes. Additionally or alternatively, generating features may include generating features related to the pathogenicity of taxa and/or products attributed to taxa. However, frame S120 may include the generation of any other suitable features of sequencing and mapping of nucleic acids derived from biological samples. For example, features may be combined (e.g., involving pairs, three groups), associated (e.g., related to the association between different features) and/or related to changes in features (e.g., time changes, changes across sample sites, etc., spatial changes, etc.). However, processing biological samples, generating microbial data sets and/or other aspects associated with frame S110 may be performed in any suitable manner.
4.2处理补充数据集4.2 Processing of Supplementary Datasets
方法100可以附加地或可替代地包括框S120,框S120可以包括处理(例如,接收、收集、转换等)针对用户集合与一种或多种微生物有关状况(例如,诸如与用户行为相关联的人类行为状况;诸如相关联的病史、症状、用药的疾病有关状况;等)(例如,提供其信息的;描述;其指示;等)相关联的补充数据集。框S120可以起到获取与受试者集合中的一个或多个受试者相关的数据的作用,该数据可以用于训练、验证、应用和/或以其他方式告知微生物有关表征过程(例如,在框S130中)。在框S120中,补充数据集优选地包括调查衍生数据,但是可以附加地或可替代地包括以下任何一项或多项:特定位点数据(例如,提供不同收集位点的信息的数据,等)、微生物有关状况数据(例如,提供微生物有关状况的信息数据,等)、从传感器衍生的前后关系的数据(contextual data)(例如,可穿戴设备数据,等)、医疗数据(例如,当前和历史的医疗数据;医疗设备衍生数据;与医学测试相关联的数据;等)、社交媒体数据、用户数据(例如,相关联传感器数据、人口统计学数据,等)、移动电话数据(例如,移动电话应用程序数据,等)、网络应用程序数据、先验生物学知识(例如,提供微生物有关状况、微生物组特性、微生物组特性和微生物有关状况之间的关联的信息,等)和/或任何其他合适类型的数据。在包括接收调查衍生数据的框S120的变型中,调查衍生数据优选地提供与受试者相关联的生理信息、人口统计学信息和行为信息。生理信息可以包括与生理特征(例如,身高、体重、体质指数、体脂百分比、体毛水平等)有关的信息。人口统计学信息可以包括与人口统计学特征(例如,性别、年龄、种族、婚姻状况、兄弟姐妹数量、社会经济地位、性取向等)有关的信息。行为信息可以包括与以下一项或多项有关的信息:健康状况(例如,健康和疾病状态)、生活状况(例如,单独生活、与宠物一起生活、与重要他人一起生活、与儿童一起生活等)、饮食习惯(例如,酒精消耗,咖啡因消耗,杂食,素食,严格素食,糖消耗,酸消耗,小麦、蛋、大豆、坚果、花生、贝类和/或其他合适食品项目的消耗,等)、行为倾向(例如,体育活动水平、药物使用、饮酒、习惯养成等)、不同移动性水平(例如,诸如低、中和/或极端体育锻炼活动的锻炼量;与在给定时间段内行进的距离有关;由诸如运动和/或位置传感器的移动性传感器指示的;等)、不同性活动水平(例如,与伴侣的数量和性取向有关)以及任何其他合适的行为信息。调查衍生数据可以包括定量数据和/或可转换为定量数据的定性数据(例如,使用严重性程度、将定性响应映射到定量分值,等)。Method 100 may additionally or alternatively include block S120, which may include processing (e.g., receiving, collecting, converting, etc.) a supplemental data set associated with one or more microbe-related conditions (e.g., human behavior conditions such as associated user behavior; disease-related conditions such as associated medical history, symptoms, medication, etc.) for the user set (e.g., providing information thereof; description thereof; indication thereof; etc.). Block S120 may function to obtain data associated with one or more subjects in the subject set, which may be used to train, validate, apply, and/or otherwise inform a microbe-related characterization process (e.g., in block S130). In block S120, the supplemental data set preferably includes survey-derived data, but may additionally or alternatively include any one or more of the following: site-specific data (e.g., data providing information about different collection sites, etc.), microbial-related condition data (e.g., data providing information about microbial-related conditions, etc.), contextual data derived from sensors (e.g., wearable device data, etc.), medical data (e.g., current and historical medical data; medical device-derived data; data associated with medical tests; etc.), social media data, user data (e.g., associated sensor data, demographic data, etc.), mobile phone data (e.g., mobile phone application data, etc.), web application data, prior biological knowledge (e.g., information providing microbial-related conditions, microbiome characteristics, associations between microbiome characteristics and microbial-related conditions, etc.), and/or any other suitable type of data. In a variation of block S120 that includes receiving survey-derived data, the survey-derived data preferably provides physiological information, demographic information, and behavioral information associated with the subject. The physiological information may include information related to physiological characteristics (e.g., height, weight, body mass index, body fat percentage, body hair level, etc.). Demographic information may include information related to demographic characteristics (e.g., gender, age, race, marital status, number of siblings, socioeconomic status, sexual orientation, etc.). Behavioral information may include information related to one or more of the following: health conditions (e.g., health and disease states), living situations (e.g., living alone, living with pets, living with significant others, living with children, etc.), dietary habits (e.g., alcohol consumption, caffeine consumption, omnivorous, vegetarian, vegan, sugar consumption, acid consumption, consumption of wheat, eggs, soy, nuts, peanuts, shellfish, and/or other suitable food items, etc.), behavioral tendencies (e.g., physical activity levels, drug use, alcohol consumption, habit formation, etc.), different mobility levels (e.g., amount of exercise such as low, moderate, and/or extreme physical exercise activities; related to distance traveled in a given time period; indicated by mobility sensors such as motion and/or location sensors; etc.), different sexual activity levels (e.g., related to number of partners and sexual orientation), and any other suitable behavioral information. Survey-derived data may include quantitative data and/or qualitative data that may be converted to quantitative data (eg, using severity levels, mapping qualitative responses to quantitative scores, etc.).
在促进调查衍生数据的接收中,框130可包括向受试者群体中的一个受试者、或向与受试者群体中的一个受试者相关联的实体提供一个或多个调查。可以当面(例如,与样品提供和从受试者接收相协调地)、电子地(例如,在由受试者设置账户期间,在受试者的电子设备上执行的应用程序中,在通过互联网连接可访问的网络应用程序中,等)和/或以其他任何合适的方式提供调查。In facilitating receipt of survey-derived data, block 130 may include providing one or more surveys to a subject in the subject population, or to an entity associated with a subject in the subject population. Surveys may be provided in person (e.g., in coordination with sample provision and receipt from the subject), electronically (e.g., during account setup by the subject, in an application executed on the subject's electronic device, in a web application accessible via an Internet connection, etc.), and/or in any other suitable manner.
附加地或可替代地,补充数据集的部分可以衍生自与受试者相关联的传感器(例如,可穿戴计算设备的传感器、移动设备的传感器、与用户相关联的生物计量传感器,等)。这样,框S130可以包括接收以下一项或多项:体育活动或体育动作有关数据(例如,来自受试者的移动设备或可穿戴电子设备的加速度计和陀螺仪数据)、环境数据(例如,温度数据、海拔数据、气候数据、光照参数数据等)、患者营养或与饮食有关数据(例如,来自食品企业记录(food establishment check-in)的数据、来自分光光度分析的数据、用户输入的数据、与益生菌和/或益生元食品项目相关联的营养数据、消耗的食物类型、消耗的食物量、饮食等)、生物计量数据(例如,通过患者的移动计算设备内的传感器记录的数据、通过与患者的移动计算设备通信的可穿戴或其他外周设备记录的数据)、位置数据(例如,使用GPS元件)和任何其他合适的数据。在变型中,传感器数据可以包括在以下一项或多项中采样的数据:光学传感器(例如,图像传感器、光传感器等)、音频传感器、温度传感器、挥发性化合物传感器、重量传感器、湿度传感器、深度传感器、位置传感器(GPS接收器等)、惯性传感器(例如,加速器、陀螺仪、磁力计等)、生物统计(biometric)传感器(例如,心率传感器、指纹传感器、生物阻抗传感器等)、压力传感器、流量传感器、功率传感器(例如,霍尔效应传感器)和/或任何其他合适的传感器。Additionally or alternatively, portions of the supplemental data set may be derived from sensors associated with the subject (e.g., sensors of a wearable computing device, sensors of a mobile device, biometric sensors associated with a user, etc.). Thus, block S130 may include receiving one or more of: physical activity or physical movement related data (e.g., accelerometer and gyroscope data from a subject's mobile device or wearable electronic device), environmental data (e.g., temperature data, altitude data, climate data, light parameter data, etc.), patient nutrition or diet related data (e.g., data from a food establishment check-in, data from a spectrophotometric analysis, user input, nutritional data associated with probiotic and/or prebiotic food items, types of food consumed, amounts of food consumed, diet, etc.), biometric data (e.g., data recorded by sensors within a patient's mobile computing device, data recorded by a wearable or other peripheral device in communication with the patient's mobile computing device), location data (e.g., using a GPS element), and any other suitable data. In a variation, the sensor data may include data sampled in one or more of the following: optical sensors (e.g., image sensors, light sensors, etc.), audio sensors, temperature sensors, volatile compound sensors, weight sensors, humidity sensors, depth sensors, location sensors (GPS receivers, etc.), inertial sensors (e.g., accelerometers, gyroscopes, magnetometers, etc.), biometric sensors (e.g., heart rate sensors, fingerprint sensors, bioimpedance sensors, etc.), pressure sensors, flow sensors, power sensors (e.g., Hall effect sensors), and/or any other suitable sensors.
附加地或可替代地,补充数据集的部分可以衍生自受试者的医疗记录数据和/或临床数据。这样,补充数据集的部分可以衍生自受试者的一个或多个电子健康记录(EHR)。Additionally or alternatively, portions of the supplemental data set may be derived from the subject's medical record data and/or clinical data. Thus, portions of the supplemental data set may be derived from one or more electronic health records (EHRs) of the subject.
附加地或可替代地,框S120的补充数据集可以包括任何其他合适的诊断信息(例如,临床诊断信息),所述诊断信息可以与衍生自特征的分析相结合,以支持方法100的后续框中的受试者的表征。例如,衍生自结肠镜检查、活检、血液检查、诊断成像、其他合适的诊断程序、调查有关信息和/或任何其他合适检查的信息可以用于补充(例如,用于方法100的任何合适部分)。Additionally or alternatively, the supplemental data set of block S120 may include any other suitable diagnostic information (e.g., clinical diagnostic information) that may be combined with the analysis derived from the features to support characterization of the subject in subsequent blocks of method 100. For example, information derived from a colonoscopy, a biopsy, a blood test, diagnostic imaging, other suitable diagnostic procedures, information related to investigations, and/or any other suitable examination may be used to supplement (e.g., for use in any suitable portion of method 100).
附加地或可替代地,补充数据集可以包括疗法有关数据,该疗法有关数据包括以下一项或多项:治疗方案(regimen)、疗法类型、建议疗法、用户使用的疗法、疗法依从性(adherence)等。例如,补充数据集可以包括对建议疗法的用户依从性(例如,药物依从性、益生菌依从性、体育锻炼依从性、饮食依从性等)。然而,处理补充数据集可以以任何合适的方式执行。Additionally or alternatively, the supplemental data set may include therapy-related data, including one or more of the following: a regimen, a therapy type, a recommended therapy, a therapy used by a user, therapy adherence, etc. For example, the supplemental data set may include user adherence to a recommended therapy (e.g., medication adherence, probiotic adherence, physical exercise adherence, dietary adherence, etc.). However, processing the supplemental data set may be performed in any suitable manner.
4.3执行表征过程4.3 Execution Characterization Process
框S130可以包括,例如基于(例如,在框S110中衍生的,等)微生物数据集和/或其他合适数据(例如,补充数据集;等)、用一个或多个微生物组表征模块来应用分析技术、以针对一种或多种微生物有关状况执行表征过程(例如,预处理、特征生成、特征处理、针对多个收集位点的多位点表征、针对多种微生物有关状况的交叉条件分析、模型生成等)S130。框S130可起到识别、确定、提取和/或以其他方式处理特征和/或特征组合的作用,该特征和/或特征组合可以用于基于用户或用户组的微生物组组成(例如,微生物组组成多样性特征等)、功能(例如,微生物组功能多样性特征等)和/或其他合适的微生物组特征(例如,诸如通过用于确定微生物有关表征的表征模型的生成和应用,等)针对用户和/或用户集合来确定微生物有关表征。这样,表征过程可以用作诊断工具,该诊断工具可以基于受试者的微生物组组成和/或功能特征,关于受试者的一种或多种健康状况状态(例如,微生物有关状况状态)、行为特质、医疗状况、人口统计学特质和/或任何其他合适的特质来表征受试者(例如,依据行为特质(behavioral trait)、依据医疗状况、依据人口统计学特质等)。这些表征可以用于确定、建议和/或提供疗法(例如,诸如通过疗法模型确定的个性化疗法,等)和/或以其他方式促进治疗干预。Block S130 may include, for example, applying analysis techniques with one or more microbiome characterization modules to perform characterization processes (e.g., preprocessing, feature generation, feature processing, multi-site characterization for multiple collection sites, cross-condition analysis for multiple microbiome-related conditions, model generation, etc.) S130 based on (e.g., derived in block S110, etc.) a microbiome dataset and/or other suitable data (e.g., a supplemental dataset; etc.). Block S130 may function to identify, determine, extract, and/or otherwise process features and/or feature combinations that may be used to determine microbiome-related characterizations for a user and/or user set based on the microbiome composition (e.g., microbiome composition diversity features, etc.), function (e.g., microbiome functional diversity features, etc.) of the user or user group, and/or other suitable microbiome features (e.g., such as by generating and applying a characterization model for determining microbiome-related characterizations, etc.). In this way, the characterization process can be used as a diagnostic tool that can characterize a subject (e.g., by behavioral trait, by medical condition, by demographic trait, etc.) based on the subject's microbiome composition and/or functional characteristics, with respect to one or more health status states (e.g., microbiome-related status states), behavioral traits, medical conditions, demographic traits, and/or any other suitable traits of the subject. These characterizations can be used to determine, suggest, and/or provide therapy (e.g., personalized therapy such as determined by a therapy model, etc.) and/or otherwise facilitate therapeutic intervention.
执行表征过程S130可以包括预处理微生物数据集、微生物组特征和/或其他合适的数据,以促进下游处理(例如,确定微生物有关表征等)。在一个实施例中,执行表征过程可以包括通过以下至少一项来过滤微生物数据集(例如,诸如在应用分析技术集合以确定微生物组特征之前,过滤微生物序列数据集,等):a)去除对应于(例如,与一种或多种微生物有关状况相关联的,等)生物样品集合的第一样品离群值(outlier)的第一样品数据,诸如其中第一样品离群值由主成分分析、降维技术和多变量方法论的至少之一确定;b)去除对应于生物样品集合的第二样品离群值的第二样品数据,其中,第二样品离群值可基于针对微生物组特征集合的相应数据质量来确定(例如,去除对应于具有低于阈值条件的高质量数据的若干微生物组特征的样品,等);和c)基于不满足阈值样品数量条件的微生物组特征的样品数量,从微生物组特征集合中去除一个或多个微生物组特征,其中样品数量对应于与微生物组特征的高质量数据相关联的样品数量。然而,可以使用任何合适的分析技术、以任何合适的方式执行预处理。Performing the characterization process S130 may include preprocessing the microbial data set, microbial group features, and/or other suitable data to facilitate downstream processing (e.g., determining microbial related features, etc.). In one embodiment, performing the characterization process may include filtering the microbial data set (e.g., such as filtering the microbial sequence data set before applying the analysis technology set to determine the microbial group features, etc.) by at least one of the following: a) removing first sample data corresponding to a first sample outlier of the biological sample set (e.g., associated with one or more microbial related conditions, etc.), such as where the first sample outlier is determined by at least one of principal component analysis, dimensionality reduction technology, and multivariate methodology; b) removing second sample data corresponding to a second sample outlier of the biological sample set, wherein the second sample outlier can be determined based on the corresponding data quality for the microbial group feature set (e.g., removing samples corresponding to several microbial group features with high-quality data below a threshold condition, etc.); and c) removing one or more microbial group features from the microbial group feature set based on the number of samples of the microbial group features that do not meet the threshold sample number condition, wherein the number of samples corresponds to the number of samples associated with high-quality data of the microbial group features. However, pre-processing may be performed in any suitable manner using any suitable analysis technique.
在执行表征过程中,框S130可以使用计算方法(例如,统计方法、机器学习方法、人工智能方法、生物信息学方法等)来将受试者表征为表现与一种或多种微生物有关状况相关联的特征(例如,具有一种或多种微生物有关状况的用户集合的特征特性,等)。In performing the characterization process, box S130 can use computational methods (e.g., statistical methods, machine learning methods, artificial intelligence methods, bioinformatics methods, etc.) to characterize the subject as exhibiting characteristics associated with one or more microbial-related conditions (e.g., characteristic characteristics of a set of users having one or more microbial-related conditions, etc.).
框S130优选地包括以一个或多个微生物组表征模块来应用一种或多种分析技术(例如,用于确定微生物组特征、生成微生物有关表征,等)。例如,应用分析技术集合来确定微生物组特征集合可以包括例如,基于微生物序列数据集等)确定微生物组特征的初始集合(;和以微生物组表征模块集合的第一微生物组表征模块(例如,分析模块B等)、在微生物组特征的初始集合上应用一种或多种降维技术以确定微生物组特征集合(例如,其中微生物组特征集合包括比微生物组特征的初始集合更少的微生物组特征,等),诸如其中降维技术可以包括缺失值比、主成分分析、概率主成分分析、矩阵分解技术、成分混合模型和特征嵌入技术中的至少一项。在一实施例中,确定微生物组特征的初始集合可以包括以微生物组表征模块集合的第二微生物组表征模块(例如,分析模块A等)、应用一个或多个统计检验(例如,单变量统计检验、多变量等)以例如,基于微生物序列数据集等)确定微生物组特征的初始集合(,例如其中统计检验(例如,单变量统计检验、多变量等)可包括t检验、柯尔莫哥洛夫-斯米尔诺夫检验和回归模型的至少之一。在一实施例中,方法100可以包括以微生物组表征模块集合的第二微生物组表征模块(例如,分析模块C等)、应用机器学习方法(和/或其他合适的人工智能方法等)以确定微生物组特征集合的相关性分值,其中生成微生物有关状况模型可以包括基于微生物组特征集合和相关性分值生成微生物有关状况模型(例如,用于确定一种或多种微生物有关状况的表征等)。Box S130 preferably includes applying one or more analysis techniques (e.g., for determining microbiome features, generating microbial-related representations, etc.) with one or more microbiome characterization modules. For example, applying a set of analysis techniques to determine a set of microbiome features may include, for example, determining an initial set of microbiome features (based on a microbial sequence data set, etc.) with a first microbiome characterization module (e.g., analysis module B, etc.) of a set of microbiome characterization modules, applying one or more dimensionality reduction techniques on the initial set of microbiome features to determine a set of microbiome features (e.g., wherein the set of microbiome features includes fewer microbiome features than the initial set of microbiome features, etc.), such as wherein the dimensionality reduction technique may include at least one of a missing value ratio, a principal component analysis, a probabilistic principal component analysis, a matrix decomposition technique, a component mixture model, and a feature embedding technique. In one embodiment, determining an initial set of microbiome features may include determining an initial set of microbiome features with a second microbiome characterization module (e.g., analysis module A, etc.) of a set of microbiome characterization modules. ), applying one or more statistical tests (e.g., univariate statistical tests, multivariate, etc.) to, for example, determine an initial set of microbiome features based on a microbial sequence data set, etc.), for example, wherein the statistical test (e.g., univariate statistical test, multivariate, etc.) may include at least one of a t-test, a Kolmogorov-Smirnov test, and a regression model. In one embodiment, method 100 may include a second microbiome characterization module (e.g., analysis module C, etc.) in a microbiome characterization module set, applying a machine learning method (and/or other suitable artificial intelligence methods, etc.) to determine a correlation score of a microbiome feature set, wherein generating a microbiome-related condition model may include generating a microbiome-related condition model based on the microbiome feature set and the correlation score (e.g., for determining a characterization of one or more microbiome-related conditions, etc.).
执行表征过程(和/或方法100和/或系统200的其他合适的部分)可以针对任何合适类型和/或数量的微生物有关状况。在一变型中,执行表征过程可以针对一种或多种皮肤有关状况。在一个例中,对于与一种或多种皮肤有关状况(例如,皮肤光敏性;头皮屑;皮肤干燥;存在(presence);不存在(absence);等)相关联的受试者,方法100可以包括:确定微生物数据集(例如,从来自生物样品的测序微生物核酸生成的微生物序列数据集,该微生物样品为受试者、诸如在不同收集位点收集,等);以及用微生物组表征模块集合中的微生物组表征模块(例如,分析模块A等),基于对应于受试者不同收集位点的微生物数据集,应用多个统计检验(例如,柯尔莫哥洛夫-斯米尔诺夫、β-二项式回归和零膨胀β-二项式回归检验、单变量统计检验、多变量统计检验等)来确定微生物组特征子集,各微生物组特征子集对应于不同的收集位点、不同的微生物有关状况(例如,不同的皮肤有关状况等)、不同的所应用的统计检验(例如,如表1、表2、表3、表4和表5所示,等)、不同的这些实体和/或任何其他合适实体的组合。在该实施例中,执行表征过程可以包括用微生物组表征模块集合的第二微生物组表征模块(例如,分析模块B等),应用降维技术(例如,有监督的和/或无监督的降维技术等)来获取从微生物组特征(例如,微生物组特征、微生物数据集等)计算的距离矩阵,其中此类数据可与机器学习方法(和/或其他合适的人工智能方法)一起使用以选择特征的子集(例如,针对一种或多种微生物有关状况的最相关特征,等)。在特定实施例中,执行表征过程可以包括:确定特征相关性分值和/或与特征重要性相关联的其他合适指标(例如,通过应用随机森林技术);以及使用特征相关性分值和/或其他合适指标与补充数据(例如,提供微生物组特征的信息的先验生物学知识,诸如用第三微生物组表征模块、分析模块F等)以(例如,使用任何合适的软件工具)获得微生物组功能特征的样品水平量化。在另一特定实施例中,诸如基于所分析样品上的微生物组功能特征和子系统的主成分的丰度概况之间的一个或多个关联系数的确定,将微生物组特征可以整合到(例如,诸如通过软件分配而分配到,等)微生物组子系统中(例如,微生物组特征的聚合、微生物组特征的组,等)。The characterization process (and/or other suitable parts of the method 100 and/or system 200) may be performed for any suitable type and/or number of microorganism-related conditions. In a variation, the characterization process may be performed for one or more skin-related conditions. In one example, for a subject associated with one or more skin-related conditions (e.g., skin photosensitivity; dandruff; dry skin; presence; absence; etc.), method 100 may include: determining a microbial dataset (e.g., a microbial sequence dataset generated from sequenced microbial nucleic acids from a biological sample, the microbial sample being the subject, such as collected at different collection sites, etc.); and using a microbiome characterization module in a microbiome characterization module set (e.g., analysis module A, etc.), based on the microbial datasets corresponding to different collection sites of the subject, applying multiple statistical tests (e.g., Kolmogorov-Smirnov, β-binomial regression and zero-inflated β-binomial regression tests, univariate statistical tests, multivariate statistical tests, etc.) to determine a microbiome feature subset, each microbiome feature subset corresponding to a different collection site, a different microbiome-related condition (e.g., different skin-related conditions, etc.), a different applied statistical test (e.g., as shown in Tables 1, 2, 3, 4, and 5, etc.), a different combination of these entities and/or any other suitable entities. In this embodiment, performing the characterization process may include using a second microbiome characterization module (e.g., analysis module B, etc.) of the microbiome characterization module set to apply a dimensionality reduction technique (e.g., supervised and/or unsupervised dimensionality reduction technique, etc.) to obtain a distance matrix calculated from microbiome features (e.g., microbiome features, microbial data sets, etc.), wherein such data can be used with a machine learning method (and/or other suitable artificial intelligence method) to select a subset of features (e.g., the most relevant features for one or more microbial related conditions, etc.). In a specific embodiment, performing the characterization process may include: determining a feature relevance score and/or other suitable indicators associated with feature importance (e.g., by applying a random forest technique); and using the feature relevance score and/or other suitable indicators with supplemental data (e.g., prior biological knowledge that provides information about microbiome features, such as using a third microbiome characterization module, analysis module F, etc.) to obtain (e.g., using any suitable software tool) sample-level quantification of microbiome functional features. In another particular embodiment, microbiome features can be integrated into (e.g., assigned, such as by software assignment, etc.) microbiome subsystems (e.g., aggregations of microbiome features, groups of microbiome features, etc.), such as based on determination of one or more correlation coefficients between microbiome functional features on analyzed samples and abundance profiles of principal components of the subsystems.
在另一变型中,执行表征过程可以为针对一种或多种胃肠道有关状况。在一实施例中,对于与一种或多种胃肠道有关状况(例如,炎性肠病;存在;不存在;等)相关联的受试者,方法100可以包括:确定微生物数据集(例如,对应于不同的收集位点;等);以及用微生物组表征模块集合的微生物组表征模块,基于对应于受试者不同收集位点的微生物数据集、应用多个统计检验(例如,柯尔莫哥洛夫-斯米尔诺夫、β-二项式回归和零膨胀β-二项式回归检验等)来确定微生物组特征子集,各微生物组特征子集对应于不同的收集位点、不同的微生物有关状况(例如,不同的皮肤有关状况等)、不同的所应用的统计检验(例如,如表15、表16、表17、表18和表19所示,等)、不同的这些实体和/或任何其他合适实体的组合(例如,其中可以比较不同的个体结果,诸如用以识别针对给定收集位点和微生物有关状况跨不同的所应用的统计检验的微生物组特征的交集,如图18所示,其分别示出了484和141微生物组特征的并集和交集,等)。在该实施例中,执行表征过程可以包括:用微生物组表征模块集合的第二微生物组表征模块(例如,分析模块B等)、应用降维技术(例如,有监督的和/或无监督的降维技术等)来构建微生物组特征之间的相关网络,其可用于例如通过合适的软件工具和/或安装包(package)、识别相互关联的特征的集合(例如,微生物组子系统等)。在该实施例中,执行表征过程可以包括针对各微生物组子系统(例如,每个相互关联的微生物组特征集合等)确定总结变量(summary variable),例如通过应用PCA方法来针对每个样品获得单一数字,该单一数字为受试者针对包括在微生物组子系统中的微生物组特征总结微生物组特征(例如,微生物组概况等)。在该实施例中,软件工具和/或其他合适的技术可以用于网络构建和微生物组子系统检测,例如用于凭经验地确定适当的分析参数。在特定实施例中,对于软阈值功率,可以选择介于1和20之间的可能值集合(例如,选择2的功率值以描述保持高连接性和相对清晰的子系统检测的网络,等),例如图19所示,其描述了从应用微生物组表征模块(例如,分析模块B等)获得的降维的代表,在该微生物组表征模块上,所检测的各微生物组子系统由不同灰度的颜色表示。应用降维技术可以导致:以主成分集合为例的原始数据(例如,用于各微生物组子系统之一)的低维代表,其中降维可达到47.7x倍(例如,约两个数量级;通过将最初考虑用于分析的430个微生物组特征转换为9个变量;等);和各微生物组特征与所识别的微生物组子系统之间的直接映射(例如,如表20所示,其描述了所获得的映射,在该映射上,每个微生物组特征被分配至微生物组子系统,并且还根据所分析样品上的特征和子系统主成分之间的相关性获得了软分配;等)。在该实施例中,执行表征过程可以包括用微生物组表征模块集合的第三微生物组表征模块(例如,分析模块F)、利用补充数据(例如,微生物组特征的先验生物学知识等)以获得微生物组功能特征的样品水平定量(例如,在合适的软件工具上实施),以便整合到微生物组子系统中,用于通过计算所分析样品上的微生物组功能特征和子系统的主成分的丰度概况之间的相关系数来获得微生物组功能特征到微生物组子系统的软分配(例如,如表21所示)。微生物组表征模块的输出(例如,降维技术的输出;分析模块B的输出)可用于生成、执行和/或以其他方式处理一个或多个机器学习模型(例如,其中分析模块B的输出可用作分析模块C和/或其他合适的微生物组表征模块的输入,等)。在一特定实施例中,微生物组子系统主成分可以用作炎性肠病状况的预测因子,其具有两个标签:报告状况的案例(case)、和不报告具有状况的对照,其中可以生成机器学习分类器(例如,随机森林分类器),用于确定特征相关性分值和/或其他特征重要性指标(例如,用于确定最重要的微生物组子系统的主成分预测因子(predictor)等)。在该特定实施例中,如表22所示,特征重要性指标识别了编号为5、2、6、0、3、1、4、7、8的不同微生物组子系统的相关性等级,其中微生物组子系统5被识别为最相关,其特征重要性比第二个更具预测性的子系统大~1.5倍、比最预测性最差的子系统大~10倍,其中与子系统5相关联的微生物组特征在表23中表示,并且与子系统5更紧密相关联的微生物组功能特征显示于表24,并且其中分类法和功能之间的相互作用的图形表示可参见图20。补充数据可以由微生物组表征模块(例如,分析模块F)使用,其中微生物组特征与小分子和药物代谢之间关系的先验生物学知识可以用于识别可能影响与子系统5、其他微生物组子系统和/或其他合适的微生物组特征相关联的可能影响代谢的药物,其中在该特定实施例中,子系统5的22个微生物组特征中6个对代谢总共12个分子和药物有作用(例如,如表25所示),其中12个分子中有4个对炎症(例如,与炎性肠病相关联的,等)有作用,并且其中这样的过程可以识别相关分子以确定药物治疗的选择,如在阿卡波糖、以及饮食和生活方式改变的情况下、如在白藜芦醇、牛磺酸和类黄酮的情况下,和/或以其他方式促进治疗干预。在特定实施例中,确定表征可包括,诸如基于微生物有关状况模型、来自用户的样品、微生物组特征集合和药物代谢之间的已知关联、和/或任何其他合适的数据,确定与一种或多种微生物有关状况相关联的药物代谢表征。In another variation, the characterization process may be performed for one or more gastrointestinal tract-related conditions. In one embodiment, for a subject associated with one or more gastrointestinal tract-related conditions (e.g., inflammatory bowel disease; presence; absence; etc.), method 100 may include: determining a microbial dataset (e.g., corresponding to different collection sites; etc.); and using a microbiome characterization module of a microbiome characterization module set to determine a microbiome feature subset based on the microbial dataset corresponding to the different collection sites of the subject, applying multiple statistical tests (e.g., Kolmogorov-Smirnov, β-binomial regression and zero-inflated β-binomial regression test, etc.), each microbiome feature subset Corresponding to different collection sites, different microbial-related conditions (e.g., different skin-related conditions, etc.), different applied statistical tests (e.g., as shown in Tables 15, 16, 17, 18, and 19, etc.), different combinations of these entities and/or any other suitable entities (e.g., where different individual results can be compared, such as to identify the intersection of microbiome features across different applied statistical tests for a given collection site and microbial-related condition, as shown in FIG. 18 , which shows the union and intersection of 484 and 141 microbiome features, respectively, etc.). In this embodiment, performing the characterization process may include: using a second microbiome characterization module (e.g., analysis module B, etc.) of the microbiome characterization module set, applying a dimensionality reduction technique (e.g., supervised and/or unsupervised dimensionality reduction technique, etc.) to construct a correlation network between microbiome features, which can be used, for example, through a suitable software tool and/or installation package (package), to identify a collection of interrelated features (e.g., microbiome subsystems, etc.). In this embodiment, performing the characterization process may include determining a summary variable for each microbiome subsystem (e.g., each interrelated microbiome feature set, etc.), such as by applying a PCA method to obtain a single number for each sample, the single number being a subject summarizing the microbiome features (e.g., microbiome profiles, etc.) for the microbiome features included in the microbiome subsystem. In this embodiment, software tools and/or other suitable techniques may be used for network construction and microbiome subsystem detection, such as for empirically determining appropriate analysis parameters. In a particular embodiment, for a soft threshold power, a possible value set between 1 and 20 may be selected (e.g., a power value of 2 is selected to describe a network that maintains high connectivity and relatively clear subsystem detection, etc.), such as shown in Figure 19, which describes a representative of the dimensionality reduction obtained from applying a microbiome characterization module (e.g., analysis module B, etc.), on which each microbiome subsystem detected is represented by a color of different grayscales. Applying dimensionality reduction techniques can result in: a low-dimensional representation of the original data (e.g., for one of each microbiome subsystem) as an example of a set of principal components, where the dimensionality reduction can be up to 47.7x times (e.g., about two orders of magnitude; by converting the 430 microbiome features originally considered for analysis into 9 variables; etc.); and a direct mapping between each microbiome feature and the identified microbiome subsystem (e.g., as shown in Table 20, which describes the obtained mapping, on which each microbiome feature is assigned to a microbiome subsystem, and a soft assignment is also obtained based on the correlation between the feature and the subsystem principal component on the analyzed sample; etc.). In this embodiment, performing the characterization process may include using a third microbiome characterization module (e.g., analysis module F) of the microbiome characterization module set, utilizing supplementary data (e.g., prior biological knowledge of microbiome features, etc.) to obtain sample-level quantification of microbiome functional features (e.g., implemented on a suitable software tool) for integration into the microbiome subsystem for obtaining a soft assignment of microbiome functional features to microbiome subsystems by calculating correlation coefficients between the abundance profiles of the principal components of the subsystem and the microbiome functional features on the analyzed samples (e.g., as shown in Table 21). The output of the microbiome characterization module (e.g., the output of the dimensionality reduction technique; the output of the analysis module B) may be used to generate, execute and/or otherwise process one or more machine learning models (e.g., where the output of the analysis module B may be used as input to the analysis module C and/or other suitable microbiome characterization modules, etc.). In a particular embodiment, microbiome subsystem principal components can be used as predictors of inflammatory bowel disease conditions, which have two labels: cases reporting the condition, and controls not reporting the condition, wherein a machine learning classifier (e.g., a random forest classifier) can be generated to determine feature relevance scores and/or other feature importance indicators (e.g., principal component predictors for determining the most important microbiome subsystems, etc.). In this particular embodiment, as shown in Table 22, the feature importance indicators identify the relevance levels of different microbiome subsystems numbered 5, 2, 6, 0, 3, 1, 4, 7, 8, wherein microbiome subsystem 5 is identified as the most relevant, with a feature importance of ~1.5 times greater than the second more predictive subsystem and ~10 times greater than the least predictive subsystem, wherein microbiome features associated with subsystem 5 are represented in Table 23, and microbiome functional features more closely associated with subsystem 5 are shown in Table 24, and wherein a graphical representation of the interaction between taxonomy and function can be seen in Figure 20. The supplemental data can be used by a microbiome characterization module (e.g., analysis module F), where prior biological knowledge of the relationship between microbiome features and small molecule and drug metabolism can be used to identify drugs that may affect metabolism associated with subsystem 5, other microbiome subsystems, and/or other suitable microbiome features, where in this particular embodiment, 6 of the 22 microbiome features of subsystem 5 have an effect on metabolism of a total of 12 molecules and drugs (e.g., as shown in Table 25), where 4 of the 12 molecules have an effect on inflammation (e.g., associated with inflammatory bowel disease, etc.), and where such a process can identify relevant molecules to determine the selection of drug treatments, such as in the case of acarbose, and dietary and lifestyle changes, such as in the case of resveratrol, taurine, and flavonoids, and/or otherwise facilitate therapeutic intervention. In particular embodiments, determining a characterization may include determining a drug metabolism characterization associated with one or more microbiome-associated conditions, such as based on a microbiome-associated condition model, a sample from a user, a known association between a microbiome feature set and drug metabolism, and/or any other suitable data.
在变型中,执行表征过程可以包括执行与多个收集位点相关联的一个或多个多位点分析(例如,用微生物组表征模块;生成多位点表征等)。例如,确定微生物有关表征(例如,针对一个或多个微生物有关状况等)可以包括:从用户收集对应于多个收集位点的位点多样性样品集合,该收集位点包括肠道、生殖器、口、皮肤和鼻中的至少两个;(例如,使用利用微生物有关状况模块生成的微生物有关状况模型,等)基于位点多样性样品集合确定位点方面的疾病倾向性指标集合,其中位点方面的疾病倾向性指标集合中的各位点方面的疾病倾向性指标对应于多个收集位点中的不同收集位点(例如,并且与一种或多种微生物有关状况相关联,等);以及基于位点方面的疾病倾向性指标集合、针对用户确定总体疾病倾向性指标(例如,其中总体疾病倾向性指标与一种或多种微生物有关状况相关联。在该实施例中,方法100可包括基于位点多样性样品集合确定与多个收集位点相关联的微生物数据集,其中确定总体疾病倾向性指标可包括:基于微生物数据集确定协方差指标和关联性指标中的至少一个,其中协方差指标和关联性指标中的至少一个与多个收集位点相关联;和基于位点方面的疾病倾向性指标集合、以及协方差指标和关联性指标中的至少一个,针对用户确定总体疾病倾向性指标。然而,多位点分析可以以任何合适的方式执行。In a variation, performing the characterization process may include performing one or more multi-site analyses associated with multiple collection sites (e.g., using a microbiome characterization module; generating a multi-site characterization, etc.). For example, determining a microbiome-related characterization (e.g., for one or more microbiome-related conditions, etc.) may include: collecting a site-diversity sample set corresponding to multiple collection sites from a user, the collection sites including at least two of the intestines, genitals, mouth, skin, and nose; (e.g., using a microbiome-related condition model generated using a microbiome-related condition module, etc.) determining a site-wise disease propensity indicator set based on the site-diversity sample set, wherein each site-wise disease propensity indicator in the site-wise disease propensity indicator set corresponds to a different collection site in the multiple collection sites (e.g., and is associated with one or more microbiome-related conditions, etc.); and determining a site-wise disease propensity indicator set based on the site-diversity sample set, An overall disease propensity index is determined for a user (e.g., where the overall disease propensity index is associated with one or more microbial-related conditions. In this embodiment, method 100 may include determining a microbial dataset associated with multiple collection sites based on a site diversity sample set, where determining the overall disease propensity index may include: determining at least one of a covariance index and an association index based on the microbial dataset, where at least one of the covariance index and the association index is associated with multiple collection sites; and determining an overall disease propensity index for the user based on the site-wise disease propensity index set and at least one of the covariance index and the association index. However, the multi-site analysis may be performed in any suitable manner.
在变型中,执行表征过程可以包括针对多个微生物有关状况(例如使用微生物组表征模块等)执行一种或多种交叉条件分析。在一实施例中,方法100可以包括针对报告26种(和/或其他合适数量的)不同微生物有关状况的受试者分析元数据和微生物组特性(例如,微生物组组成、功能等),该26种不同的微生物有关状况中的一种或多种包括酒渣鼻、乳糜泻、光敏性、小麦过敏、麸质不耐受(例如,麸质过敏等)、乳制品过敏、腹胀、类风湿性关节炎、炎性肠综合症(IBS)、痔疮疾病、便秘、反流、多发性硬化症、骨关节炎、溃疡性结肠炎、克罗恩病、腹泻、大豆过敏、花生过敏、树坚果过敏、蛋类过敏、牛皮癣、桥本氏甲状腺炎、格雷夫氏病、炎性肠病和血便。微生物组表征模块(例如,分析模块B和分析模块C等)可应用于构建预测模型,该预测模型提供特定状况特征和多状况特征(例如,跨多种微生物有关状况共享的,等)的信息,其中执行交叉条件分析可以包括,例如基于多条件特征确定微生物组相关参数,该微生物组相关参数告知两种状况之间共享的微生物有关状况相关联的程度。执行交叉条件分析可以包括:将降维技术应用于从微生物组特性(例如,微生物组特征、微生物数据集等)计算出的距离矩阵;以及以机器学习模型和/或其他合适的人工智能方法使用潜在变量。在一特定实施例中,执行交叉条件分析可包括(例如,针对对应于不同受试者的不同样品,等)确定微生物组特征之间的布雷-柯蒂斯(Bray-Curtis)差异;将所得到的样品相异度矩阵应用为奇异值分解的输入,以衍生出主成分和本征值;以及对解释超过数据总方差的1/1000的主成分执行附加的分析。可以执行后续的交叉条件分析,例如包括,用微生物组表征模块(例如,分析模块C)应用机器学习模型和/或其他合适的人工智能方法、诸如贝叶斯多核回归来获得由微生物组特性解释的交叉条件关联性的定量。执行交叉条件分析可以包括使用多变量方差成分模型定量由微生物组特性解释的状况之间的关联性、以及由微生物组特征解释的微生物有关状况之间的协方差,该多变量方差成分模型估计与微生物组相关的各微生物有关状况(例如,表型)的方差。在一特定实施例中,执行交叉条件分析可包括拟合以下形式的二元方差成分模型:y=u+u0+u1+∈,其中u1~N(0,G1),其中且 并且其中u0捕获由定量的对两种表型的共同作用,而u1捕获由和定量的表型特定作用。在特定实施例中,表型的协方差可被构造为导致的微生物组介导的相关估计,针对各特质由微生物组解释的表型方差的分数分别为和在特定实施例中,可以将共相关(co-correlation)计算为共类似于定量遗传学术语中的共遗传性。对于任一特质,x可以对应于从样品Bray-Curtis相似性矩阵的奇异值分解获得的主成分的子集。可以使用合适的软件工具来拟合模型。性别、年龄和/或其他合适的用户数据可以作为固定效应协变量(fixed-effect covariate)包括在分析中。在另一实施例中,方法100可以包括确定多条件微生物组特征,其中确定多条件微生物组特征包括用微生物组表征模块集合的第一微生物组表征模块(例如,分析模块B等)、将降维技术应用于基于微生物序列数据集确定的微生物组特征的初始集合;用微生物组表征模块集合的第二微生物组表征模块、确定多个微生物有关状况的不同状况之间的交叉条件关联指标;并且基于该交叉条件关联指标、多条件微生物组特征集合和来自用户的样品,确定多条件表征。在该实施例中,针对用户确定多条件表征可以包括基于多个微生物有关状况中的当前用户状况(例如,基于微生物有关状况之间的共病性、基于微生物有关状况之间的关联性;等)、多条件微生物组特征集合、来自用户的样品和交叉条件关联指标,确定多个微生物有关状况中的附加的用户状况的表征。在该实施例中,用第二微生物组表征模块确定交叉条件关联指标可包括针对多个微生物有关状况中的不同状况,应用多变量模型、典型关联模型和多标签人工智能方法中的至少一种。然而,可以以任何合适的方式来执行,确定交叉条件关联指标、与交叉条件分析相关联的其他合适指标和/或执行其他合适的交叉条件分析。In variations, performing the characterization process may include performing one or more cross-condition analyses for a plurality of microbiome-related conditions (e.g., using a microbiome characterization module, etc.). In one embodiment, method 100 may include analyzing metadata and microbiome characteristics (e.g., microbiome composition, functionality, etc.) for subjects reporting 26 (and/or other suitable number of) different microbiome-related conditions, one or more of the 26 different microbiome-related conditions including rosacea, celiac disease, photosensitivity, wheat allergy, gluten intolerance (e.g., gluten sensitivity, etc.), dairy allergy, bloating, rheumatoid arthritis, inflammatory bowel syndrome (IBS), hemorrhoidal disease, constipation, reflux, multiple sclerosis, osteoarthritis, ulcerative colitis, Crohn's disease, diarrhea, soy allergy, peanut allergy, tree nut allergy, egg allergy, psoriasis, Hashimoto's thyroiditis, Grave's disease, inflammatory bowel disease, and bloody stools. The microbiome characterization module (e.g., analysis module B and analysis module C, etc.) can be applied to build a predictive model that provides information about specific condition features and multi-condition features (e.g., shared across multiple microbial-related conditions, etc.), wherein performing cross-condition analysis can include, for example, determining microbiome-related parameters based on the multi-condition features, which tell the degree to which the shared microbial-related conditions between two conditions are associated. Performing cross-condition analysis can include: applying dimensionality reduction techniques to a distance matrix calculated from microbiome characteristics (e.g., microbiome features, microbial datasets, etc.); and using latent variables with machine learning models and/or other suitable artificial intelligence methods. In a specific embodiment, performing cross-condition analysis can include determining Bray-Curtis differences between microbiome features (e.g., for different samples corresponding to different subjects, etc.); applying the resulting sample dissimilarity matrix as input to a singular value decomposition to derive principal components and eigenvalues; and performing additional analysis on principal components that explain more than 1/1000 of the total variance of the data. Subsequent cross-conditional analysis can be performed, for example, including applying a machine learning model and/or other suitable artificial intelligence method, such as Bayesian multi-kernel regression, with a microbiome characterization module (e.g., analysis module C) to obtain quantification of cross-conditional associations explained by microbiome characteristics. Performing the cross-conditional analysis can include quantifying the associations between conditions explained by microbiome characteristics and the covariance between microbial-related conditions explained by microbiome characteristics using a multivariate variance component model that estimates the variance of each microbial-related condition (e.g., phenotype) associated with the microbiome. In a specific embodiment, performing the cross-conditional analysis can include fitting a binary variance component model of the following form: y=u+u 0 +u 1 +∈, where u 1 ~N(0,G 1 ), in and and where u 0 captures the quantifies the joint effect on the two phenotypes, while u1 captures the and Quantitative phenotype-specific effects. In certain embodiments, the covariance of the phenotype can be constructed as lead to The microbiome-mediated correlation estimates for each trait are and In certain embodiments, co-correlation can be calculated as Similar to co-inheritance in quantitative genetics terms. For any trait, x can correspond to a subset of principal components obtained from the singular value decomposition of the sample Bray-Curtis similarity matrix. Suitable software tools can be used to fit the model. Gender, age and/or other suitable user data can be included in the analysis as fixed-effect covariates. In another embodiment, method 100 may include determining multi-conditional microbiome features, wherein determining multi-conditional microbiome features includes using a first microbiome characterization module (e.g., analysis module B, etc.) of a microbiome characterization module set, applying a dimensionality reduction technique to an initial set of microbiome features determined based on a microbial sequence data set; using a second microbiome characterization module of a microbiome characterization module set, determining a cross-conditional association index between different conditions of a plurality of microbial-related conditions; and based on the cross-conditional association index, a multi-conditional microbiome feature set and a sample from a user, determining a multi-conditional characterization. In this embodiment, determining a multi-conditional characterization for a user may include determining a characterization of additional user conditions in a plurality of microorganism-related conditions based on a current user condition in a plurality of microorganism-related conditions (e.g., based on comorbidity between microorganism-related conditions, based on correlation between microorganism-related conditions; etc.), a multi-conditional microbiome feature set, a sample from a user, and a cross-conditional correlation index. In this embodiment, determining a cross-conditional correlation index with a second microbiome characterization module may include applying at least one of a multivariate model, a typical correlation model, and a multi-label artificial intelligence method for different conditions in a plurality of microorganism-related conditions. However, it may be performed in any suitable manner to determine a cross-conditional correlation index, other suitable indicators associated with a cross-conditional analysis, and/or perform other suitable cross-conditional analyses.
执行交叉条件分析可以包括识别微生物有关状况的组(例如,集群),例如具有共享的微生物组特性(例如,共享的微生物组关联,等)的相似模式的微生物有关状况的组。例如,方法100可以包括:基于多条件微生物组特征(例如,使用微生物组表征模块确定的,等),确定来自多个微生物有关状况的微生物有关状况组集合;和基于微生物有关状况组集合(例如,和多条件表征,等),促进针对微生物有关状况的治疗干预。在一实施例中,识别组可以包括:执行无监督的层次聚类(hierarchical clustering),其中输入可包括成比例的关联矩阵通过行之间的斯皮尔曼相关(Spearman correlation)计算距离矩阵以估计行的距离;以及将距离矩阵用作层次聚类的输入。在该实施例中,贝叶斯多核回归可用于识别由微生物数据(例如,微生物组特征)解释的表型方差的实质性但可变分数(fraction),其中,在一特定实施例中,所解释的方差(R2)的范围从对溃疡性结肠炎的63%到对光敏性的10%(例如,如图21和表26所示)。在该实施例中,多变量混合模型的应用可以被用于估计325对疾病之间的微生物组有关关联性co-r12,其中结果可用于使用基于微生物组的关联性的聚类分析以获得正在分析的微生物有关状况的数据驱动排列(例如,如图22和25所示),并且其中分层组织可导致六个微生物有关状况组(例如,聚类,如表27所示;如图25所示,其中沿对角线的数字表明在给定组内具有共病性的个体,例如其中它们报告相同组的微生物有关状况,并且其中非对角线的数字表明具有跨组的共病性的个体,诸如报告对应于非对角线点的各组的至少一种状况;等)。可以识别统计上有意义的条件对。在该实施例中,多重检验校正可导致将325个中的75个(23%)识别为显著相关联的关联性(邦费罗尼(Bonferroni)校正的p值<0.05),其可包括15对的10对中的75个组间关联中的52个(69%),其中聚类V和聚类VI具有比预期更聚类间(intercluster)显著的相关性(二项式p值=2×10-10;观察的=76%,30个中的23个;预期的=24%,325个中的79个),并且其中这些聚类由自身免疫和过敏状况(例如,其中相关性的总结可显示于表27中,等)表征。在实施例中,交叉条件分析可指示疾病共病性,诸如关于人类肠道微生物组和/或对应于其他位点的其他合适的微生物组,等)。在实施例中,衍生数据支持人类肠道微生物组与多种状况(例如,共病状况,等)之间的关联,诸如其中衍生数据可以显示微生物组,该微生物组解释在多种自身免疫疾病的情况下方差的显著变化(例如,对于溃疡性结肠炎,R2=0.69;对于桥本氏甲状腺炎,R2=0.49;对于克罗恩病,R2=0.69;等)。Performing cross-condition analysis can include identifying groups (e.g., clusters) of microbial-related conditions, such as groups of microbial-related conditions that have similar patterns of shared microbial group characteristics (e.g., shared microbial group associations, etc.). For example, method 100 can include: determining a set of microbial-related condition groups from multiple microbial-related conditions based on multi-conditional microbial group features (e.g., determined using a microbial group characterization module, etc.); and facilitating therapeutic intervention for microbial-related conditions based on the set of microbial-related condition groups (e.g., and multi-condition characterizations, etc.). In one embodiment, identifying the group can include: performing unsupervised hierarchical clustering, where the input can include a proportional association matrix A distance matrix is calculated by Spearman correlation between rows to estimate the distance of the rows; and the distance matrix is used as input for hierarchical clustering. In this embodiment, Bayesian multiple kernel regression can be used to identify a substantial but variable fraction of phenotypic variance explained by microbial data (e.g., microbiome signatures), wherein in a particular embodiment, the explained variance (R 2 ) ranges from 63% for ulcerative colitis to 10% for photosensitivity (e.g., as shown in FIG. 21 and Table 26). In this embodiment, application of multivariate mixed models can be used to estimate microbiome-related associations co- r12 between 325 pairs of diseases, where the results can be used to use cluster analysis based on microbiome associations to obtain a data-driven arrangement of the microbiome-related conditions being analyzed (e.g., as shown in Figures 22 and 25), and where the hierarchical organization can result in six groups of microbiome-related conditions (e.g., clusters, as shown in Table 27; as shown in Figure 25, where numbers along the diagonal indicate individuals with comorbidity within a given group, e.g., where they report the same group of microbiome-related conditions, and where numbers off-diagonal indicate individuals with comorbidity across groups, such as reporting at least one condition for each group corresponding to the off-diagonal points; etc.). Statistically significant pairs of conditions can be identified. In this embodiment, multiple testing correction can result in identifying 75 of 325 (23%) associations as significantly associated (Bonferroni-corrected p-value < 0.05), which can include 52 of 75 between-group associations (69%) in 10 of 15 pairs where Cluster V and Cluster VI have a more intercluster significant correlation than expected (binomial p-value = 2× 10-10 ; observed = 76%, 23 of 30; expected = 24%, 79 of 325), and where these clusters are characterized by autoimmune and allergic conditions (e.g., where a summary of the correlations can be shown in Table 27, etc.). In embodiments, cross-conditional analyses can indicate disease comorbidity, such as with respect to the human gut microbiome and/or other suitable microbiomes corresponding to other sites, etc.). In embodiments, the derived data supports associations between the human gut microbiome and multiple conditions (e.g., comorbid conditions, etc.), such as where the derived data may show a microbiome that explains significant variation in variance in the context of multiple autoimmune diseases (e.g., R 2 =0.69 for ulcerative colitis; R 2 =0.49 for Hashimoto's thyroiditis; R 2 =0.69 for Crohn's disease; etc.).
在该实施例中,交叉条件分析可以导致六个微生物有关状况组的识别:聚类I(例如,如表28所示,关于共现(co-occurrence),等),其包括小麦和麸质有关障碍、以及酒渣鼻和皮肤光敏性;聚类II,其包括乳制品过敏(例如,如表29所示,等)、类风湿性关节炎(rheumatoid arthritis,RA)和腹胀;聚类III,其包括肠易激综合症(IBS)(例如,如表30所示,关于与炎症性肠病(inflammatory bowel disease,IBD)和其他微生物有关状况的共现,等)、反流、便秘和痔疮;聚类IV,其包括多发性硬化症(multiple sclerosis,MS)和骨关节炎(osteoarthritis,OA);聚类V,其包括溃疡性结肠炎和克罗恩病、IBD的两种亚型、和在两种状况中普遍存在的症状性腹泻;聚类VI,其包括剩余的(remaining)食物过敏(例如,大豆过敏、花生过敏、树坚果过敏和蛋类过敏)和自身免疫性疾病(例如,牛皮癣、桥本氏甲状腺炎、格雷夫病和IBD)。在一实施例中,微生物有关状况组集合可以包括以下至少之一:第一组,其包括过敏有关状况;第二组,其包括运动有关(locomotor-related)状况;和第三组,其包括胃肠道有关状况,并且其中促进治疗干预可包括基于多条件表征和第一、第二与第三组中的至少之一(例如,基于将微生物有关状况分类为聚类,等)来促进针对微生物有关状况的治疗干预。在一实施例中,可以计算具有不同数量的共病的女性和男性的分数(例如,如表31所示)。In this example, the cross-condition analysis can lead to the identification of six microbiome-related condition groups: Cluster I (e.g., as shown in Table 28, for co-occurrence, etc.), which includes wheat and gluten-related disorders, as well as rosacea and skin photosensitivity; Cluster II, which includes dairy allergy (e.g., as shown in Table 29, etc.), rheumatoid arthritis (RA), and bloating; Cluster III, which includes irritable bowel syndrome (IBS) (e.g., as shown in Table 30, for co-occurrence with inflammatory bowel disease (IBD) and other microbiome-related conditions, etc.), reflux, constipation, and hemorrhoids; Cluster IV, which includes multiple sclerosis (MS), and inflammatory bowel disease (IBD). Cluster V includes ulcerative colitis and Crohn's disease, two subtypes of IBD, and symptomatic diarrhea that is common in both conditions; Cluster VI includes remaining food allergies (e.g., soy allergy, peanut allergy, tree nut allergy, and egg allergy) and autoimmune diseases (e.g., psoriasis, Hashimoto's thyroiditis, Grave's disease, and IBD). In one embodiment, the set of microbial-related condition groups may include at least one of the following: a first group including allergy-related conditions; a second group including locomotive-related conditions; and a third group including gastrointestinal-related conditions, and wherein promoting therapeutic intervention may include promoting therapeutic intervention for microbial-related conditions based on multi-condition characterization and at least one of the first, second, and third groups (e.g., based on classifying microbial-related conditions into clusters, etc.). In one embodiment, scores for women and men with different numbers of comorbidities may be calculated (e.g., as shown in Table 31).
执行交叉条件分析可在促进治疗干预中使用。执行交叉条件分析可用于分组微生物有关状况以识别生物学相关的状况组,其可通过在用户的微生物组特征和共病状况的风险上对用户进行分层,来促进治疗干预,诸如用于包括初级防御、早期筛查、个性化疗法的发展和/或任何其他合适疗法应用的多水平治疗干预。微生物有关状况的微生物组驱动分类(例如,聚类等)可以使得用户分层,用于促进预防、诊断、治疗和/或其他合适的治疗干预有关过程,诸如用于优先安排疗法和/或改进相同组的状况和/或劝阻在组当中显示出相反结果的疗法。例如,促进治疗干预可包括以下至少一项:a)基于将用户分配到(例如,使用本文中描述的分析技术,通过一个或多个微生物组表征模块识别的;等)微生物有关状况组集合中的至少一个微生物有关状况组,针对用户推广(promoting)第一疗法;b)基于属于微生物有关状况组集合中的相同微生物有关状况组的微生物有关状况之间的关联,针对用户推广第二疗法;和c)基于属于微生物有关状况组集合中的不同微生物有关状况组的微生物有关状况之间的关联,针对用户劝阻第三疗法。然而,可以以任何合适的方式使用交叉条件分析和/或任何其他合适的表征过程以促进治疗干预。Performing cross-condition analysis can be used in facilitating therapeutic intervention. Performing cross-condition analysis can be used to group microbial-related conditions to identify biologically related groups of conditions, which can facilitate therapeutic interventions by stratifying users on their microbial group characteristics and the risk of comorbid conditions, such as for multi-level therapeutic interventions including primary defense, early screening, development of personalized therapies, and/or any other suitable therapeutic applications. Microbiome-driven classification (e.g., clustering, etc.) of microbial-related conditions can stratify users for facilitating prevention, diagnosis, treatment, and/or other suitable therapeutic intervention-related processes, such as for prioritizing therapies and/or improving conditions in the same group and/or discouraging therapies that show opposite results among the group. For example, promoting a therapeutic intervention may include at least one of the following: a) promoting a first therapy for a user based on assigning the user to at least one microbe-related condition group in a set of microbe-related condition groups (e.g., identified by one or more microbe group characterization modules using analysis techniques described herein; etc.); b) promoting a second therapy for a user based on associations between microbe-related conditions belonging to the same microbe-related condition group in the set of microbe-related condition groups; and c) discouraging a third therapy for a user based on associations between microbe-related conditions belonging to different microbe-related condition groups in the set of microbe-related condition groups. However, cross-condition analysis and/or any other suitable characterization process may be used in any suitable manner to promote therapeutic intervention.
在一变型中,表征可以基于与表现出目标状态(例如,微生物有关状况状态)的第一组受试者和未表现出目标状态(例如,“正常”状态)的第二组受试者之间的相似点和/或差异的统计分析(例如,概率分布的分析)相关联(例如,从其衍生)的特征。在实施该变型中,可以使用柯尔莫哥洛夫-斯米尔诺夫(KS)检验、置换检验、克莱默-冯米塞斯(Cramér-vonMises)检验、任何其他统计检验(例如,t检验、z检验、卡方(chi-squared)检验、与分布相关联的检验)和/或其他合适的分析技术中的一种或多种。特别地,一种或多种这样的统计假设检验可用于评估在表现出目标状态(例如,患病状态)的第一组受试者和未表现出目标状态(例如,具有正常状态)的第二组受试者中具有不同丰度的特征集合。。更详细地,可以基于与第一组受试者和第二组受试者相关联的百分比丰度和/或属于多样性的任何其他合适参数,来约束所评估的特征集合,以便增加或降低表征置信度(confidence)。在该实施例的特定实施方式中,特征可以衍生自细菌的分类单元,该细菌的分类单元在第一组受试者和第二组受试者一定百分比中为丰富,其中第一组受试者和第二组受试者之间的分类的相对丰度可从KS检验中确定,具有显著性指示(例如,以p值表示)。因此,框S130的输出可以包括标准化的相对丰度值(例如,具有微生物有关状况的受试者相比于没有微生物有关状况的受试者中,分类单元的风度大25%;患病受试者相比于健康受试者),具有显著性指示(例如,p值为0.0013)。特征生成的变化可以附加地或可替代地实施或衍生自功能特征或元数据特征(例如,非细菌标志物)。附加地或可替代地,可以基于统计分析(例如,应用于微生物序列数据集和/或其他合适的微生物数据集等)衍生出任何合适的微生物组特征,该统计分析包括以下任何一项或多项:预测分析、多假设测试、随机森林检验、主成分分析和/或其他合适的分析技术。In one variation, the characterization can be based on features associated with (e.g., derived from) statistical analysis (e.g., analysis of probability distribution) of similarities and/or differences between a first group of subjects that exhibit a target state (e.g., a microbial-related condition) and a second group of subjects that do not exhibit the target state (e.g., a "normal" state). In implementing this variation, one or more of a Kolmogorov-Smirnov (KS) test, a permutation test, a Cramer-von Mises test, any other statistical test (e.g., a t-test, a z-test, a chi-squared test, a test associated with a distribution), and/or other suitable analytical techniques can be used. In particular, one or more such statistical hypothesis tests can be used to evaluate a set of features that have different abundances in a first group of subjects that exhibit a target state (e.g., a diseased state) and a second group of subjects that do not exhibit the target state (e.g., having a normal state). . In more detail, the evaluated feature set can be constrained based on the percentage abundance associated with the first group of subjects and the second group of subjects and/or any other suitable parameter belonging to diversity, so as to increase or decrease the characterization confidence (confidence). In a specific implementation of this embodiment, the feature can be derived from a taxon of bacteria, which is abundant in a certain percentage of the first group of subjects and the second group of subjects, wherein the relative abundance of the classification between the first group of subjects and the second group of subjects can be determined from the KS test, with a significant indication (e.g., expressed as a p-value). Therefore, the output of box S130 can include standardized relative abundance values (e.g., the demeanor of the taxon is 25% greater in subjects with microbial-related conditions compared to subjects without microbial-related conditions; sick subjects compared to healthy subjects), with a significant indication (e.g., p-value is 0.0013). The changes in feature generation can be implemented or derived from functional features or metadata features (e.g., non-bacterial markers) in addition or alternatively. Additionally or alternatively, any suitable microbiome signature can be derived based on statistical analysis (e.g., applied to a microbial sequence dataset and/or other suitable microbial dataset, etc.), the statistical analysis comprising any one or more of the following: predictive analysis, multiple hypothesis testing, random forest testing, principal component analysis, and/or other suitable analytical techniques.
在执行表征过程中,框S130可以附加地或可替代地将来自微生物组组成多样性数据集和微生物组功能多样性数据集的至少一个的输入数据转换成特征向量,可以测试该特征向量在预测受试者群体表征中的功效。来自补充数据集的数据可用于提供表征集合的一个或多个表征的指示,其中表征过程使用候选特征和候选分类的训练数据集进行训练,以识别在准确预测分类中具有高度(或低度)预测能力的特征和/或特征组合。这样,利用训练数据集的表征过程的细化识别出与受试者的特定分类具有高度关联性的特征集(例如,受试者特征、特征组合)。In performing the characterization process, block S130 may additionally or alternatively convert input data from at least one of the microbiome compositional diversity dataset and the microbiome functional diversity dataset into a feature vector that may be tested for efficacy in predicting a subject population characterization. Data from the supplemental dataset may be used to provide an indication of one or more characterizations of a characterization set, wherein the characterization process is trained using a training dataset of candidate features and candidate classifications to identify features and/or feature combinations that have a high (or low) predictive power in accurately predicting a classification. In this way, refinement of the characterization process using the training dataset identifies a set of features (e.g., subject features, feature combinations) that are highly correlated with a particular classification of a subject.
在变型中,在预测表征过程的分类中有效的特征向量(和/或任何合适的特征集)可以包括与以下一项或多项有关的特征:微生物组多样性指标(例如,关于跨分类组的分布,关于跨古生菌、细菌、病毒和/或真核生物组的分布)、在一个个体的微生物组中分类组的存在、在一个个体的微生物组中的特定遗传序列(例如,16S序列)的表示、一个个体的微生物组中分类组的相对丰度、微生物组适应力(resilience)指标(例如,响应于从补充数据集确定的扰动)、编码具有给定功能的蛋白质或RNA(例如,酶、转运蛋白、来自免疫系统的蛋白质、激素、干扰RNA等)的基因的丰度、以及与微生物组多样性数据集和/或补充数据集相关联(例如,从其衍生)的任何其他合适的特征。在变型中,微生物组特征可以与以下至少一项相关联(例如,包括、对应于、代表等):来自微生物组特征(例如,用户微生物组特征等)的微生物组特征的存在、来自微生物组特征的微生物组特征的不存在、与微生物有关状况相关联的不同分类组的相对丰度;与不同分类组相关的至少两个微生物组特征之间的比例、不同分类组之间的相互作用以及不同分类组之间的系统发育距离。在一特定实施例中,微生物组特征可以包括一种或多种相对丰度特性,该相对丰度特性与微生物组组成多样性特性(例如,与不同分类群相关联的相对丰度等)和微生物组功能多样性特征(例如,对应于不同功能特征的序列相对丰度;等)的至少一个相关联。相对丰度特性和/或其他合适的微生物组特征(和/或本文中描述的其他合适的数据)可以基于以下进行提取和/或以其他方式确定:标准化、衍生自线性潜在变量分析和非线性潜在变量分析的至少之一的特征向量、线性回归、非线性回归、核方法、特征嵌入方法、机器学习方法、统计推断方法和/或其他合适的分析技术。附加地或可替代地,可以在特征向量中使用特征的组合,其中可以在提供组合的特征作为特征集的一部分中分组和/或加权特征。例如,一个特征或特征集可以包括一个个体的微生物组中代表的细菌种类的数量的加权合成、一个个体的微生物组中细菌的特定属的存在、一个个体的微生物组中特定的16S序列的表示、和第一门细菌对第二门细菌的相对丰度。然而,特征向量可以附加地或可替代地以任何其他合适的方式确定。In variations, feature vectors (and/or any suitable set of features) effective in the classification of the predictive characterization process may include features related to one or more of: microbiome diversity indicators (e.g., regarding distribution across taxonomic groups, regarding distribution across archaea, bacteria, viruses and/or eukaryotic groups), the presence of taxonomic groups in the microbiome of an individual, representation of specific genetic sequences (e.g., 16S sequences) in the microbiome of an individual, the relative abundance of taxonomic groups in the microbiome of an individual, microbiome resilience indicators (e.g., in response to perturbations determined from supplementary datasets), the abundance of genes encoding proteins or RNAs with a given function (e.g., enzymes, transporters, proteins from the immune system, hormones, interfering RNAs, etc.), and any other suitable features associated with (e.g., derived from) a microbiome diversity dataset and/or a supplementary dataset. In a variation, a microbiome feature may be associated with (e.g., include, correspond to, represent, etc.) at least one of the following: the presence of a microbiome feature from a microbiome feature (e.g., a user microbiome feature, etc.), the absence of a microbiome feature from a microbiome feature, the relative abundance of different taxonomic groups associated with a microbial-related condition; the ratio between at least two microbiome features associated with different taxonomic groups, the interaction between different taxonomic groups, and the phylogenetic distance between different taxonomic groups. In a particular embodiment, a microbiome feature may include one or more relative abundance characteristics associated with at least one of a microbiome composition diversity feature (e.g., relative abundance associated with different taxonomic groups, etc.) and a microbiome functional diversity feature (e.g., relative abundance of sequences corresponding to different functional features; etc.). Relative abundance characteristics and/or other suitable microbiome features (and/or other suitable data described herein) may be extracted and/or otherwise determined based on: standardization, feature vectors derived from at least one of linear latent variable analysis and nonlinear latent variable analysis, linear regression, nonlinear regression, kernel methods, feature embedding methods, machine learning methods, statistical inference methods, and/or other suitable analysis techniques. Additionally or alternatively, a combination of features can be used in a feature vector, where the features can be grouped and/or weighted in providing the combined features as part of a feature set. For example, a feature or feature set can include a weighted synthesis of the number of bacterial species represented in an individual's microbiome, the presence of a particular genus of bacteria in an individual's microbiome, the representation of a particular 16S sequence in an individual's microbiome, and the relative abundance of a first phylum of bacteria to a second phylum of bacteria. However, a feature vector can be additionally or alternatively determined in any other suitable manner.
如图3所示,在框S130的一个这样的可替代变型中,可以根据随机森林预测因子(random forest predictor,RFP)算法来生成和训练表征过程,RFP算法将装袋(bagging)(例如,自助聚合(bootstrap aggregation))和来自训练数据集的随机特征集合的选择结合,以构建与随机特征集合相关联的决策树集合T。在使用随机森林算法中,来自决策树集合的N个案例随机采样,进行替换以创建决策树的子集,并且针对各节点,从所有预测特征中选择m个预测特征进行评估。在节点处(例如,根据目标函数)提供最佳分割的预测特征用于执行分割(例如,在节点处分割为双叉(bifurcation),在节点处分割为三叉(trifurcation))。通过从大型数据集中采样多次,可以在识别预测分类中强的特征方面大幅度提高表征过程的强度。在该变型中,可以在处理期间包括为了防止偏差(例如,采样偏差)和/或解决偏差量的措施,诸如以增加模型的稳健性(robustness)。As shown in FIG. 3 , in one such alternative variation of box S130, a characterization process can be generated and trained according to a random forest predictor (RFP) algorithm, which combines bagging (e.g., bootstrap aggregation) with the selection of a random feature set from a training data set to construct a decision tree set T associated with the random feature set. In using the random forest algorithm, N cases from a decision tree set are randomly sampled with replacement to create a subset of decision trees, and for each node, m prediction features are selected from all prediction features for evaluation. The prediction features that provide the best segmentation at the node (e.g., according to the objective function) are used to perform segmentation (e.g., segmentation at the node into bifurcation and segmentation at the node into trifurcation). By sampling multiple times from a large data set, the strength of the characterization process can be greatly improved in terms of identifying strong features in the prediction classification. In this variation, measures to prevent bias (e.g., sampling bias) and/or address the amount of bias can be included during processing, such as to increase the robustness of the model.
在一种变型中,框S130和/或方法100的其他部分可以包括将计算机实施规则(例如,模型、特征选择规则等)应用于处理群体水平数据,但是可以附加地或可替代地包括将计算机实施规则应用于,在特定人口统计学基础上(例如,共享诸如治疗方案、饮食方案、体育活动方案、种族、年龄、性别、体重、睡眠行为的人口统计学特征的亚组)、在特定状况基础上(例如,表现出特定微生物有关状况的亚组、微生物有关状况的组合、微生物有关状况的触发因素、相关联症状,等)、在样品特定类型的基础上(例如,将不同计算机实施规则应用于处理衍生自不同收集位点的微生物组数据;等)、在用户基础上(例如,针对不同用户的不同计算机实施规则)和/或任何其他合适的基础上,处理微生物组有关数据。这样,框S130可以包括将来自用户群体的用户分配到一个或多个亚组;和应用不同计算机实施规则来针对不同亚组确定特征(例如,所使用的特征类型集合;从特征生成的表征模型的类型;等)。然而,应用计算机实施规则可以以任何合适的方式来执行。In one variation, block S130 and/or other portions of method 100 may include applying computer-implemented rules (e.g., models, feature selection rules, etc.) to process population-level data, but may additionally or alternatively include applying computer-implemented rules to process microbiome-related data on a specific demographic basis (e.g., a subgroup that shares demographic characteristics such as treatment regimens, dietary regimens, physical activity regimens, race, age, gender, weight, sleep behavior), on a specific condition basis (e.g., a subgroup that exhibits a specific microbiome-related condition, a combination of microbiome-related conditions, triggers of microbiome-related conditions, associated symptoms, etc.), on a sample-specific type basis (e.g., applying different computer-implemented rules to process microbiome data derived from different collection sites; etc.), on a user basis (e.g., different computer-implemented rules for different users), and/or any other suitable basis. Thus, block S130 may include assigning users from a user population to one or more subgroups; and applying different computer-implemented rules to determine features for different subgroups (e.g., a set of feature types used; a type of characterization model generated from the features; etc.). However, applying computer-implemented rules may be performed in any suitable manner.
在另一变型中,框S130可包括处理(例如,生成、训练、更新、执行、存储等)用于一个或多个微生物有关状况(例如,用于针对用户输出描述关于微生物有关状况的用户微生物组特性的表征,等)的一个或多个表征模型(例如,微生物有关状况表征模型等)。表征模型优选利用微生物组特征作为输入,并且优选输出微生物有关表征和/或其任何合适的成分;但是可以使用表征模型且合适的输入以生成任何合适的输出。在一实施例中,框S130可以包括将补充数据、微生物组组成多样性特征和微生物组功能多样性特征、其他微生物组特征、微生物组表征模块的输出和/或其他合适的数据针对一种或多种微生物有关状况转换成一个或多个表征模型(例如,基于补充数据和微生物组特征训练微生物有关表征模型;等)。在另一实施例中,方法100可以包括:基于来自用户群体的样品集合,针对与一种或多种微生物有关状况相关联的用户群体确定群体微生物序列数据集(例如,包括针对该群体的不同用户的微生物序列输出;等);针对受试者群体收集与一种或多种微生物有关状况的诊断相关联的补充数据集;和基于群体微生物序列数据集和补充数据集,生成微生物有关状况表征模型。In another variation, block S130 may include processing (e.g., generating, training, updating, executing, storing, etc.) one or more characterization models (e.g., microbe-related condition characterization models, etc.) for one or more microbe-related conditions (e.g., for outputting a characterization of a user's microbiome characteristics regarding a microbe-related condition to a user, etc.). The characterization model preferably utilizes microbiome features as input, and preferably outputs microbe-related characterizations and/or any suitable components thereof; however, the characterization model and suitable inputs may be used to generate any suitable output. In one embodiment, block S130 may include converting supplemental data, microbiome compositional diversity features and microbiome functional diversity features, other microbiome features, outputs of a microbiome characterization module, and/or other suitable data into one or more characterization models for one or more microbe-related conditions (e.g., training a microbe-related characterization model based on supplemental data and microbiome features; etc.). In another embodiment, method 100 may include: determining a population microbial sequence dataset for a user population associated with one or more microbial-related conditions (e.g., including microbial sequence outputs for different users of the population; etc.) based on a set of samples from a user population; collecting a supplementary dataset associated with the diagnosis of one or more microbial-related conditions for a subject population; and generating a microbial-related condition characterization model based on the population microbial sequence dataset and the supplementary dataset.
在另一变型中,如图8A-8C所示,可以针对不同的微生物有关状况、不同的用户人口统计特征(demographics)(例如,基于年龄、性别、体重、身高、种族;等)、不同的生理学位点(例如,肠道位点模型、鼻位点模型、皮肤位点模型、口位点模型、生殖器位点模型等)、个人用户、补充数据(例如,结合微生物组特征、微生物有关状况、和/或其他合适成分的先前的知识的模型;与生物统计传感器数据和/或调查响应数据相关联的特征相比于独立于补充数据的模型,等)、和/或其他合适的标准,生成不同的微生物有关表征模型和/或其他合适的模型(例如,用不同算法、用不同特征集合、用不同输入和/或输出类型生成的,以诸如关于时间、频率、应用模型的组件的不同方式应用的,等)。In another variation, as shown in FIGS. 8A-8C , different microbiome-related characterization models and/or other suitable models (e.g., generated using different algorithms, using different feature sets, using different input and/or output types, applied in different ways such as with respect to time, frequency, components of an application model, etc.) may be generated for different microbiome-related conditions, different user demographics (e.g., based on age, gender, weight, height, race, etc.), different physiological sites (e.g., gut site model, nasal site model, skin site model, oral site model, genital site model, etc.), individual users, supplemental data (e.g., models that incorporate prior knowledge of microbiome characteristics, microbiome-related conditions, and/or other suitable components; features associated with biometric sensor data and/or survey response data versus models independent of supplemental data, etc.), and/or other suitable criteria.
在变型中,确定微生物有关表征和/或任何其他合适的表征可以包括诸如通过以下任何一项或多项确定关于特定生理位点(例如,肠道、健康的肠道、皮肤、鼻、口、生殖器、其他合适的生理位点,其他样品收集位点,等)的微生物有关表征:基于表征模型确定微生物有关表征,该表征模型基于特定位点数据衍生(例如,定义与一个或多个生理位点相关联的微生物有关状况和微生物组特征之间的关联性);基于在一个或多个生理位点、和/或任何其他合适的位点有关过程中收集的用户生物样品确定微生物有关表征。在实施例中,机器学习方法(例如,分类器、深度学习算法)、参数优化方法(例如,贝叶斯参数优化)、验证方法(例如,交叉验证方法)、统计检验(例如,单变量统计技术、多变量统计技术、诸如典型关联分析的关联分析等)、降维技术和/或其他合适的分析技术(例如,本文中描述的)可应用于确定位点有关(例如,生理位点有关,等)表征(例如,针对一个或多个样品收集位点、诸如针对各类型的样品收集位点,使用一种或多种方法,等)、其他合适的表征、疗法和/或任何其他合适的输出。在一特定实施例中,执行表征过程(例如,确定微生物有关表征;确定微生物组特征;基于微生物有关表征模型;等)可以包括应用以下至少一种:机器学习方法、参数优化方法、统计检验、降维方法和/或其他合适的方法(例如,其中诸如微生物组组成多样性特征集合和/或微生物组功能多样性特征集合的微生物组特征可以与在肠道位点、皮肤位点、鼻位点、口位点、生殖器位点至少之一处收集的微生物相关联,等)。在另一特定实施例中,针对多个样品收集位点执行的表征过程可用于生成单个表征,该单个表征可被组合以确定聚合(aggregate)表征(例如,聚合微生物组分值、诸如针对本文中描述的一种或多种状况,等)。然而,方法100可以包括确定任何合适的位点有关(例如,特定位点的)输出,和/或以任何合适的方式、用位点特异性和其他位点关系(relatedness)执行方法100的任何合适的部分(例如,收集样品、处理样品、确定疗法)。In variations, determining microbe-related characterizations and/or any other suitable characterizations can include determining microbe-related characterizations about a particular physiological site (e.g., the intestine, healthy intestine, skin, nose, mouth, genitals, other suitable physiological sites, other sample collection sites, etc.) such as by any one or more of the following: determining microbe-related characterizations based on a characterization model derived from site-specific data (e.g., defining associations between microbe-related conditions and microbiome characteristics associated with one or more physiological sites); determining microbe-related characterizations based on a user biological sample collected at one or more physiological sites, and/or any other suitable site-related process. In an embodiment, a machine learning method (e.g., a classifier, a deep learning algorithm), a parameter optimization method (e.g., a Bayesian parameter optimization), a validation method (e.g., a cross-validation method), a statistical test (e.g., a univariate statistical technique, a multivariate statistical technique, an association analysis such as a canonical association analysis, etc.), a dimensionality reduction technique, and/or other suitable analysis techniques (e.g., as described herein) may be applied to determine site-related (e.g., physiological site-related, etc.) characterizations (e.g., for one or more sample collection sites, such as for each type of sample collection site, using one or more methods, etc.), other suitable characterizations, therapies, and/or any other suitable outputs. In a particular embodiment, performing a characterization process (e.g., determining microbial-related characterizations; determining microbial group characteristics; based on a microbial-related characterization model; etc.) may include applying at least one of the following: a machine learning method, a parameter optimization method, a statistical test, a dimensionality reduction method, and/or other suitable methods (e.g., wherein microbial group characteristics such as a microbial group composition diversity feature set and/or a microbial group functional diversity feature set can be associated with microorganisms collected at at least one of an intestinal site, a skin site, a nasal site, an oral site, a genital site, etc.). In another particular embodiment, characterization processes performed for multiple sample collection sites may be used to generate a single characterization that may be combined to determine an aggregate characterization (e.g., an aggregate microbial component value, such as for one or more conditions described herein, etc.). However, method 100 may include determining any suitable site-related (e.g., site-specific) output, and/or perform any suitable portion of method 100 (e.g., collecting samples, processing samples, determining therapy) in any suitable manner, with site-specificity and other site-relatedness.
受试者的表征可以附加地或可替代地实施高假阳性检验和/或高假阴性检验的使用,以进一步分析在根据方法100的实施方式生成的支持分析中表征过程的敏感性。然而,执行表征过程S130可以以任何合适的方式执行。Characterization of the subject may additionally or alternatively implement the use of high false positive tests and/or high false negative tests to further analyze the sensitivity of the characterization process in supporting analyses generated according to embodiments of method 100. However, performing the characterization process S130 may be performed in any suitable manner.
4.3.1皮肤有关表征过程4.3.1 Skin-related characterization processes
执行表征过程S130可以包括执行皮肤有关表征过程(例如,针对一种或多种皮肤有关状况的确定表征;确定和/或应用一种或多种皮肤有关表征模型,诸如应用与一个或多个微生物组表征模块相关联的一种或多种分析技术的模型;用一个或多个微生物组表征模块应用一种或多种分析技术以针对诸如共病的皮肤有关状况生成一种或多种皮肤有关状况的皮肤有关表征;确定皮肤有关表征,以在确定和/或推广针对一种或多种皮肤有关状况的一种或多种疗法中使用;等)S135,诸如针对一个或多个用户(例如,针对对应于来自受试者集合的样品的数据,用于针对用户生成皮肤有关表征;针对单一用户,用于诸如通过使用一种或多种皮肤有关表征模型,针对该用户生成皮肤有关表征;等)和/或针对一种或多种皮肤有关状况(例如,使用任何合适类型和数量的微生物组表征模块、交叉条件分析等)。Executing the characterization process S130 may include executing a skin-related characterization process (e.g., determining characterizations for one or more skin-related conditions; determining and/or applying one or more skin-related characterization models, such as models that apply one or more analysis techniques associated with one or more microbiome characterization modules; applying one or more analysis techniques with one or more microbiome characterization modules to generate skin-related characterizations for one or more skin-related conditions, such as comorbid skin-related conditions; determining skin-related characterizations for use in determining and/or promoting one or more therapies for one or more skin-related conditions; etc.) S135, such as for one or more users (e.g., for data corresponding to samples from a collection of subjects, for generating skin-related characterizations for the users; for a single user, for generating skin-related characterizations for the user, such as by using one or more skin-related characterization models; etc.) and/or for one or more skin-related conditions (e.g., using any suitable type and number of microbiome characterization modules, cross-condition analysis, etc.).
在一变型中,执行皮肤有关表征过程可以包括确定与一种或多种皮肤有关状况相关联的微生物组特征。在一实施例中,执行皮肤有关表征过程可以包括应用一种或多种分析技术(例如,统计分析)以识别具有与一种或多种皮肤有关状况(例如,与单一皮肤有关状况相关联的特征,与多种皮肤有关状况和/或其他合适的皮肤有关状况相关联的交叉条件特征,等)的最高关联性的微生物组特征集合(例如,微生物组组成特征、微生物组组成多样性特征、微生物组功能特征、微生物组功能多样性特征等)。在一特定实施例中,执行皮肤有关表征过程可以促进针对一种或多种皮肤有关状况的治疗干预,诸如通过促进与疗法相关联的干预,该疗法对一个或多个用户关于一种或多种皮肤有关状况的状态具有积极作用。在另一特定实施例中,执行皮肤有关表征过程(例如,确定与一种或多种皮肤有关状况的最高关联的特征,等)可以基于随机森林预测因子算法,该随机森林预测因子算法用衍生自受试者群体(例如,具有一种或多种皮肤有关状况的受试者;不具有一种或多种皮肤有关状况的受试者;等)子集的训练数据集训练,并用衍生自受试者群体子集的验证数据集进行验证。然而,确定微生物组特征和/或与一种或多种皮肤有关状况相关联的其他合适的方面可以以任何合适的方式来执行。In one variation, performing the skin-related characterization process may include determining microbiome features associated with one or more skin-related conditions. In one embodiment, performing the skin-related characterization process may include applying one or more analytical techniques (e.g., statistical analysis) to identify a set of microbiome features (e.g., microbiome composition features, microbiome composition diversity features, microbiome functional features, microbiome functional diversity features, etc.) with the highest correlation with one or more skin-related conditions (e.g., features associated with a single skin-related condition, cross-condition features associated with multiple skin-related conditions and/or other suitable skin-related conditions, etc.). In a specific embodiment, performing the skin-related characterization process may facilitate therapeutic intervention for one or more skin-related conditions, such as by facilitating intervention associated with a therapy that has a positive effect on the status of one or more users with respect to the one or more skin-related conditions. In another specific embodiment, performing a skin-related characterization process (e.g., determining features with the highest association with one or more skin-related conditions, etc.) can be based on a random forest predictor algorithm trained with a training dataset derived from a subset of a subject population (e.g., subjects with one or more skin-related conditions; subjects without one or more skin-related conditions; etc.) and validated with a validation dataset derived from a subset of the subject population. However, determining microbiome features and/or other suitable aspects associated with one or more skin-related conditions can be performed in any suitable manner.
在变型中,执行皮肤有关表征过程S135可以包括针对一种或多种光敏性有关状况执行光敏性相关状况表征过程。在一实施例中,皮肤有关表征过程可以基于统计学分析来识别与光敏性相关联状况具有最高关联性的特征集合,基于用衍生自受试者群体子集的训练数据集训练的、并用衍生自受试者群体子集的验证数据集验证的随机森林预测因子算法,一种或多种疗法对该与光敏性相关联状况有积极作用。在实施例中,光敏性相关联状况特征可以包括通过皮肤对日光的电磁光谱成分的异常反应而表征的皮肤状况。在实施例中,光敏性相关联状况可以通过皮肤检查、光测试和光斑测试和/或其他合适的方法来诊断。光敏性相关联状况可以与特定微生物群多样性和/或与肠道微生物的相对丰度有关的健康状况、与任何合适的生理位点相关联的微生物、微生物组功能多样性、和/或其他合适的微生物组有关方面相关联。In a variation, performing the skin-related characterization process S135 may include performing a photosensitivity-related condition characterization process for one or more photosensitivity-related conditions. In one embodiment, the skin-related characterization process may identify a feature set with the highest correlation with a photosensitivity-associated condition based on a statistical analysis, and one or more therapies have a positive effect on the photosensitivity-associated condition based on a random forest predictor algorithm trained with a training data set derived from a subset of a subject population and validated with a validation data set derived from a subset of a subject population. In an embodiment, the photosensitivity-associated condition features may include a skin condition characterized by an abnormal response of the skin to electromagnetic spectrum components of sunlight. In an embodiment, the photosensitivity-associated condition may be diagnosed by skin examination, light testing, and light spot testing and/or other suitable methods. The photosensitivity-associated condition may be associated with a specific microbiome diversity and/or a health condition related to the relative abundance of intestinal microorganisms, microorganisms associated with any suitable physiological site, microbiome functional diversity, and/or other suitable microbiome-related aspects.
与一种或多种光敏性相关联状况(和/或其他合适的皮肤有关状况)相关联(例如,正相关;负相关;对诊断有用;等)的微生物组特征可以包括与以下分类群中的一个或多个的任意组合相关联的特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关联的功能方面的特征;描述从其衍生的特征;描述其存在和/或不存在的特征;等):拟普雷沃菌属(Alloprevotella)(属)、普雷沃菌属(Prevotella)WAL 2039G种(种)、乳腺炎棒状杆菌(Corynebacterium mastitidis)(种)、拟杆菌科(Bacteroidaceae)(科)、布劳特菌属(Blautia)(属)、拟杆菌属(Bacteroides)(属)、脱硫弧菌属(Desulfovibrio)(属)、梭菌属(Clostridium)(属)、普通拟杆菌(Bacteroides vulgatus)(种)、普拉栖粪杆菌(Faecalibacterium prausnitzii)(种)、粪布劳特菌(Blautia faecis)(种)、腐败另枝菌(Alistipes putredinis)(种)、拟杆菌AR20种(种)、拟杆菌AR29种(种)、产酸拟杆菌(Bacteroides acidifaciens)(种)、迪尔玛菌属(Dielma)(属)、斯莱克菌属(Slackia)(属)、埃格特菌属(Eggerthella)(属)、阿德勒克罗伊茨菌属(Adlercreutzia)(属)、副普雷沃菌属(Paraprevotella)(属)、另枝菌属(Alistipes)(属)、霍尔德曼氏菌属(Holdemania)(属)、艾森伯格氏菌属(Eisenbergiella)(属)、肠杆菌属(Enterorhabdus)(属)、产液阿德勒克罗伊茨菌(Adlercreutzia equolifaciens)(种)、琥珀酸考拉杆菌(Phascolarctobacterium succinatutens)(种)、食葡糖罗斯拜瑞菌(Roseburiainulinivorans)(种)、考拉杆菌377种(种)、匹格脱硫弧菌(Desulfovibrio piger)(种)、埃格特菌HGA1种(种)、内脂因子长形产乳杆菌(Lactonifactor longoviformis)(种)、另枝菌HGB5种(种)、丝状霍尔德曼氏菌(Holdemania filiformis)(种)、柯林斯肠炎胎弧菌菌(Collinsella intestinalis)(种)、猕猴奈瑟菌(Neisseria macacae)(种)、梭菌科(Clostridiaceae)(科)、血孪生球菌(Gemella sanguinis)(种)、脆弱拟杆菌(Bacteroidesfragilis)(种)、肠杆菌科(Enterobacteriaeae)(科)、毛螺菌科(Lachnospiraceae)(科)、巴斯德菌科(Pasteurellaceae)(科)、巴斯德菌目(Pasteurellales)(目)、肠杆菌目(Enterobacteriales)(目)、鞘氨醇杆菌目(Sphingobacteriales)(目)、嗜血杆菌属(Haemophilus)(属)、明串珠菌属(Leuconostoc)(属)、短波单胞菌属(Brevundimonas)(属)、口普雷沃菌(Prevotella oris)(种)、臭气杆菌属(Odoribacter)(属)、二氧化碳噬纤维菌属(Capnocytophaga)(属)、黄杆菌属(Flavobacterium)(属)、布伦纳假单胞菌(Pseudomonas brenneri)(种)、鲸黄杆菌(Flavobacterium ceti)(种)、短波单胞菌FXJ8.080种(种)、瘤胃球菌科(Ruminococcaceae)(科)、弧菌科(Vibrionaceae)(科)、黄杆菌科(Flavobacteriaceae)(科)、梭杆菌科(Fusobacteriaceae)(科)、紫单胞菌科(Porphyromonadaceae)(科)、短杆菌科(Brevibacteriaceae)(科)、红杆菌科(Rhodobacteraceae)(科)、间孢囊菌科(Intrasporangiaceae)(科)、双歧杆菌科(Bifidobacteriaceae)(科)、鞘氨醇杆菌科(Sphingobacteriaceae)(科)、柄杆菌科(Caulobacteraceae)(科)、弯曲杆菌科(Campylobacteraceae)(科)、拟杆菌纲(Bacteroidia)(纲)、梭杆菌纲(Fusobacteriia)(纲)、黄杆菌纲(Flavobacteriia)(纲)、双歧杆菌目(Bifidobacteriales)(目)、奈瑟菌目(Neisseriales)(目)、拟杆菌目(Bacteroidales)(目)、红杆菌目(Rhodobacterales)(目)、黄杆菌目(Flavobacteriales)(目)、弧菌目(Vibrionales)(目)、梭杆菌目(Fusobacteriales)(目)、柄杆菌目(Caulobacterales)(目)、梭杆菌门(Fusobacteria)(门)、放线棒菌属(Actinobaculum)(属)、小弯杆菌属(Varibaculum)(属)、镰刀链杆菌属(Fusicatenibacter)(属)、短杆菌属(Brevibacterium)(属)、粪杆菌属(Faecalibacterium)(属)、弯曲杆菌属(Campylobacter)(属)、放线杆菌属(Actinobacillus)(属)、卟啉单胞菌(Porphyromonas)(属)、梭杆菌属(Fusobacterium)(属)、金黄杆菌属(Chryseobacterium)(属)、巨球菌(Megasphaera)(属)、罗氏菌属(Rothia)(属)、奈瑟菌属(Neisseria)(属)、乳杆菌BL302种(种)、普列比乌斯拟杆菌(bacteroides plebeius)(种)、溃疡棒状杆菌(Corynebacterium ulcerans)(种)、寒武小弯杆菌(Varibaculum cambriense)(种)、韦克斯勒布劳特菌(Blautia wexlerae)(种)、葡萄球菌WB18-16种(种)、口腔分类单元链球菌(Streptococcus oral taxon)G63种(种)、疮疱丙酸杆菌(Propionibacterium acnes)(种)、厌氧球菌(Anaerococcus)9401487种(种)、副流感嗜血杆菌(Haemophilus parainfluenzae)(种)、表皮葡萄球菌(Staphylococcus epidermidis)(种)、解脲弯曲杆菌(Campylobacter ureolyticus)(种)、两面神菌(Janibacter)M3-5种(种)、蒂莫宁普雷沃菌(Prevotella timonensis)(种)、嗜胨菌(Peptoniphilus)DNF00840种(种)、芬戈尔德菌(Finegoldia)S8 F7种(种)、解糖胨普雷沃菌(Prevotella disiens)(种)、卡式卟啉单胞菌(Porphyromonas catoniae)(种)、牙周梭杆菌(Fusobacterium periodonticum)(种)、和/或其他合适的分类群(例如,本文中所述);和/或可以包括与以下一项或多项的任何组合相关的功能特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关的功能方面的特征;描述从其衍生特征;描述其存在和/或不存在的特征;等):传染性疾病(KEGG2)、表征欠佳(Poorly Characterized)(KEGG2)、代谢疾病(KEGG2)、免疫系统疾病(KEGG2)、细胞过程和信号传导(KEGG2)、限制性内切酶(KEGG3)、核苷酸切除修复(KEGG3)和/或其他合适的功能特征(例如,如本文中所述)。在变型中,用户的表征可以包括基于以对诊断和/或治疗的典型方法是附加的或可替代的方式、监测以上特征的一种或多种,将用户表征为具有一种或多种光敏性皮肤相关状况的人。Microbiome signatures associated with (e.g., positively correlated; negatively correlated; useful for diagnosis; etc.) one or more photosensitivity-associated conditions (and/or other suitable skin-related conditions) may include signatures associated with (e.g., signatures describing their abundance; signatures describing their relative abundance; signatures describing functional aspects associated with them; signatures describing derivations from them; signatures describing their presence and/or absence; etc.) any combination of one or more of the following taxa: Alloprevotella (genus), Prevotella WAL 2039G species (species), Corynebacterium mastitidis (species), Bacteroidaceae (family), Blautia (genus), Bacteroides (genus), Desulfovibrio (genus), Clostridium (genus), Bacteroides vulgatus (species), Faecalibacterium prausnitzii (species), Blautia faecis (species), Alistipes putredinis (species), Bacteroides AR20 (species), Bacteroides AR29 (species), Bacteroides acidifaciens (species), Dielma (genus), Slackia (genus), Eggerthella (genus), Adlercreutzia (genus), Paraprevotella (genus), Alistipes (genus), Holdemania (genus), Eisenbergiella (genus), Enterorhabdus (genus), Adlercreutzia equolifaciens (species), Phascolarctobacterium succinatutens (species), Roseburia inulinivorans (species), Phascolarctobacterium 377 species (species), Desulfovibrio piger (species), Eggertella HGA 1 species (species), Lactonifactor longoviformis (species), HGB 5 species (species), Holdemania filiformis (species), Collinsella intestinalis (species), Neisseria macacae (species), Clostridiaceae (family), Gemella sanguinis (species), Bacteroides fragilis (species), Enterobacteriaeae (family), Lachnospiraceae (family), Pasteurellaceae (family), Pasteurelales (order), Enterobacteriales (order), Sphingobacteriales (order), Haemophilus (genus), Leuconostoc (genus), Brevundimonas (genus), Prevotella oris (species), Odoribacter (genus), Capnocytophaga (genus), Flavobacterium (genus), Pseudomonas brenneri (species), Flavobacterium ceti)(species), Brevundimonas FXJ8.080 species(species), Ruminococcaceae(family), Vibrionaceae(family), Flavobacteriaceae(family), Fusobacteriaceae(family), Porphyromonadaceae(family), Brevibacteriaceae(family), Rhodobacteraceae(family), Intrasporangiaceae(family), Bifidobacteriaceae (Bifidobacteriaceae)(family), Sphingobacteriaceae(family), Caulobacteraceae(family), Campylobacteraceae(family), Bacteroidia(class), Fusobacteriia(class), Flavobacteriia(class), Bifidobacteriales(order), Neisseriales(order), Bacteroida les (order), Rhodobacterales (order), Flavobacteriales (order), Vibrionales (order), Fusobacteriales (order), Caulobacterales (order), Fusobacteria (phylum), Actinobaculum (genus), Varibaculum (genus), Fusicatenibacter (genus), Brevibacterium (genus), m)(genus), Faecalibacterium(genus), Campylobacter(genus), Actinobacillus(genus), Porphyromonas(genus), Fusobacterium(genus), Chryseobacterium(genus), Megasphaera(genus), Rothia(genus), Neisseria(genus), Lactobacillus BL302(species), Bacteroides plebius(genus), plebeius (species), Corynebacterium ulcerans (species), Varibaculum cambriense (species), Blautia wexlerae (species), Staphylococcus WB18-16 species (species), Streptococcus oral taxon G63 species (species), Propionibacterium acnes (species), Anaerococcus 9401487 species (species), Haemophilus parainfluenzae (species), Staphylococcus epidermidis (species), Campylobacter ureolyticus (species), Janibacter M3-5 species (species), Prevotella timoniensis (species), timonensis (species), Peptoniphilus DNF00840 (species), Finegoldia S8 F7 (species), Prevotella disiens (species), Porphyromonas catoniae (species), Fusobacterium periodonticum (species), and/or other suitable taxa (e.g., as described herein); and/or may include functional features (e.g., features describing its abundance; features describing its relative abundance; features describing functional aspects associated with it; features describing its derivation from it; features describing its presence and/or absence; etc.) associated with any combination of one or more of the following: infectious diseases (KEGG2), poorly characterized (Poorly Characterized) (KEGG2), metabolic diseases (KEGG2), immune system diseases (KEGG2), cellular processes and signaling (KEGG2), restriction endonucleases (KEGG3), nucleotide excision repair (KEGG3), and/or other suitable functional characteristics (e.g., as described herein). In a variation, the characterization of the user can include characterizing the user as a person with one or more photosensitive skin-related conditions based on monitoring one or more of the above characteristics in an additional or alternative manner to typical methods of diagnosis and/or treatment.
在变型中,执行皮肤有关表征过程S135可以包括针对一种或多种皮肤干燥相关状况执行皮肤干燥相关状况表征过程。在一实施例中,皮肤有关表征处理可以基于统计分析来识别具有与干燥皮肤相关联状况最高关联性的特征集合,基于用衍生自受试者群体子集的训练数据集训练的、并用衍生自受试者群体子集的验证数据集进行验证的随机森林预测因子算法一种或多种疗法对该干燥皮肤相关联状况有积极作用。在实施例中,皮肤干燥相关联状况可以包括以下一种或多种:皮肤粗糙、瘙痒、剥落、脱屑或脱皮、细纹或裂纹、深色皮肤个体的皮肤灰白、发红、可流血和可导致感染的深裂纹、和/或其他合适的皮肤干燥相关联状况。皮肤干燥相关联状况可以与特定微生物群多样性和/或与肠道微生物的相对丰度有关的健康状况、与任何合适的生理位点相关的微生物、微生物组功能多样性和/或其他合适的微生物组有关方面相关。In a variation, performing the skin-related characterization process S135 may include performing a dry skin-related condition characterization process for one or more dry skin-related conditions. In one embodiment, the skin-related characterization process may be based on statistical analysis to identify a feature set with the highest correlation with a dry skin-related condition, based on a random forest predictor algorithm trained with a training data set derived from a subject population subset and validated with a validation data set derived from a subject population subset, and one or more therapies have a positive effect on the dry skin-related condition. In an embodiment, the dry skin-related condition may include one or more of the following: rough skin, itching, flaking, scaling or peeling, fine lines or cracks, gray skin in dark skin individuals, redness, deep cracks that can bleed and can lead to infection, and/or other suitable dry skin-related conditions. Dry skin-related conditions may be associated with a specific microbiome diversity and/or a health condition related to the relative abundance of intestinal microorganisms, microorganisms associated with any suitable physiological site, microbiome functional diversity, and/or other suitable microbiome-related aspects.
与一种或多种皮肤干燥有关状况(和/或其他合适的皮肤有关状况)相关联(例如,正相关;负相关;对诊断有用;等)的微生物组特征可以包括与以下分类群中的一个或多个的任意组合相关的特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关的功能方面的特征;描述从其衍生自特征;描述其存在和/或不存在的特征;等):棒状杆菌科(Corynebacteriaceae)(科)、芽孢杆菌纲(Bacilli)(纲)、乳杆菌目(Lactobacillales)(目)、放线菌目(目)、厚壁菌门(Firmicutes)(门)、棒状杆菌属(Corynebacterium)(属)、皮杆菌科(Dermabacteraceae)(科)、乳杆菌科(Lactobacillaceae)(科)、丙酸杆菌科(Propionibacteriaceae)(科)、放线菌纲(Actinobacteria)(纲)、皮杆菌属(Dermabacter)(属)、戴阿利斯特杆菌属(Dialister)(属)、费克蓝姆菌属(Facklamia)(属)、乳杆菌(属)、丙酸杆菌(Propionibacterium)(属)、溃疡棒状杆菌(种)、人费克蓝姆菌(Facklamiahominis)(种)、棒状杆菌种(种)、丙酸杆菌MSP09A种(种)、费克蓝姆菌1440-97种(种)、葡萄球菌C9I2种(种)、厌氧球菌9402080种(种)、解葡萄糖苷棒状杆菌(Corynebacteriumglucuronolyticum)(种)、人皮杆菌(Dermabacter hominis)(种)、肠杆菌科(科)、假单胞菌科(Pseudomonadaceae)(科)、葡萄球菌科(Staphylococcaceae)(科)、γ-变形菌纲(Gammaproteobacteria)(纲)、芽孢杆菌目(目)、肠杆菌目(目)、双歧杆菌属(Bifidobacterium)(属)、假单胞菌属(Pseudomonas)(属)、厌氧球菌属(属)、克鲁维菌属(Kluyvera)(属)、阿托波菌属(Atopobium)(属)、葡萄球菌属(属)、乳杆菌BL302种(种)、乳腺炎棒状杆菌(种)、长双歧杆菌(Bifidobacterium longum)(种)、双子厌氧球菌种(Anaeroglobus geminatus)(种)、厌氧球菌S9 PR-16种(种)、蒂莫宁普雷沃菌(种)、乔治亚娜克鲁维菌(种)、放线棒菌属(属)、芬戈尔德菌(Finegoldia)(属)、克罗诺杆菌属(Cronobacter)(属)、不动杆菌(Acinetobacter)WB22-23种(种)、八叠厌氧球菌(Anaerococcus octavius)(种)、芬戈尔德菌S9 AA1-5种(种)、葡萄球菌C-D-MA2种(种)、嗜胨菌(Peptoniphilus)7-2种(种)、阪崎克罗诺杆菌(Cronobacter sakazakii)(种)、巴斯德菌科(科)、酸杆菌纲(Acidobacteriia)(纲)、鞘氨醇杆菌纲(Sphingobacteriia)(纲)、鞘氨醇杆菌目(目)、酸杆菌门(Acidobacteria)(门)、卟啉单胞菌(属)、嗜血杆菌属(属)、不动杆菌属(属)、厌氧球菌8405254种(种)、鞘氨醇单胞菌科(Sphingomonadaceae)(科)、鞘氨醇单胞菌目(Sphingomonadales)(目)、库克菌属(Kocuria)(属)、孪生球菌属(属)、韦荣球菌(Veillonella)CM60种(种)、乳杆菌7_1_47FAA(种)、孪生球菌933-88种(种)、卡式卟啉单胞菌(种)、副流感嗜血杆菌(种)、拟杆菌AR20种(种)、普通拟杆菌(种)、拟杆菌D22种(种)、多拉长脂链霉素菌(Dorea Longicatena)(种)、粪副拟杆菌(Parabacteroides merdae)(种)、拟杆菌AR29种(种)、多拉菌属(Dorea)(属)、柯林斯菌属(属)、拟杆菌属(属)、颤螺菌科(Oscillospiraceae)(科)、瘤胃球菌科(科)、拟杆菌科(科)、疣微菌科(Verrucomicrobiaceae)(科)、红蝽菌科(Coriobacteriaceae)(科)、梭菌目(目)、拟杆菌目(目)、疣微菌目(Verrucomicrobiales)(目)、红蝽菌目(Coriobacteriales)(目)、高温厌氧菌目(Thermoanaerobacterales)(目)、梭菌纲(Clostridia)(纲)、拟杆菌纲(纲)、疣微菌纲(Verrucomicrobiae)(纲)、疣微菌门(Verrucomicrobia)(门)、拟杆菌门(Bacteroidetes)(门)、和/或其他合适的分类群(例如,本文中所述);和/或可以包括与以下一项或多项的任何组合相关的功能特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关的功能方面的特征;描述从其衍生自特征;描述其存在和/或不存在的特征;等):转录(KEGG2)、细胞过程和信号传导(KEGG2)、氨基酸代谢(KEGG2)、细胞生长和死亡(KEGG2)、复制和修复(KEGG2)、其他氨基酸的代谢(KEGG2)、神经退行性疾病(KEGG2)、辅助因子和维生素的代谢(KEGG2)、运输和分解代谢(KEGG2)、内分泌系统(KEGG2)、免疫系统疾病(KEGG2)、排泄系统(KEGG2)、酶家族(KEGG2)、膜运输(KEGG2)、碳水化合物代谢(KEGG2)、其他次生代谢产物的生物合成(KEGG2)、萜类化合物和聚酮化合物的代谢(KEGG2)、传染性疾病(KEGG2)、遗传信息处理(KEGG2)、神经系统(KEGG2)、环境适应(KEGG2)、核苷酸代谢(KEGG2)、信号分子与相互作用(KEGG2)、信号转导(KEGG2)、无机离子的运输与代谢(KEGG3)、染色体(KEGG3)、细胞循环–柄杆菌属(KEGG3)、核糖体生物发生(KEGG3)、DNA复制蛋白(KEGG3)、转录因子(KEGG3)、甘氨酸、丝氨酸和苏氨酸代谢(KEGG3)、硫代谢(KEGG3)、其他离子耦合的转运蛋白(KEGG3)、缬氨酸、亮氨酸和异亮氨酸的生物合成(KEGG3)、氮代谢(KEGG3)、肽聚糖的生物合成(KEGG3)、同源重组(KEGG3)、过氧化物酶体(KEGG3)、硫中继系统(KEGG3)、肽酶(KEGG3)、蛋白激酶(KEGG3)、错配修复(KEGG3)、二甲苯降解(KEGG3)、核糖体(KEGG3)、RNA聚合酶(KEGG3)、色氨酸代谢(KEGG3)、组氨酸代谢(KEGG3)、维生素代谢(KEGG3)、细胞运动和分泌(KEGG3)、嘧啶代谢(KEGG3)、细胞骨架蛋白(KEGG3)、DNA复制(KEGG3)、氨基糖和核苷酸糖代谢(KEGG3)、叶酸生物合成(KEGG3)、光合生物中的碳固定(KEGG3)、磷脂酰肌醇信号传导系统(KEGG3)、赖氨酸降解(KEGG3)、硒化合物代谢(KEGG3)、果糖和甘露糖代谢(KEGG3)、肌醇磷酸代谢(KEGG3)、蛋白质折叠和相关处理(KEGG3)、氧化物酶体增殖激活受体(PPAR)信号传导途径(KEGG3)、脂质代谢(KEGG3)、缬氨酸、亮氨酸和异亮氨酸降解(KEGG3)、乙醛酸和二羧酸代谢(KEGG3)、精氨酸和脯氨酸代谢(KEGG3)、柠檬烯和蒎烯降解(KEGG3)、D-丙氨酸代谢(KEGG3)、卟啉和叶绿素代谢(KEGG3)、C5-支链二元酸代谢(KEGG3)、分子伴侣和折叠催化物(KEGG3)、脂肪酸代谢(KEGG3)、谷胱甘肽代谢(KEGG3)、磷酸戊糖途径(KEGG3)、磷酸转移酶系统(Phosphotransferase system,PTS)(KEGG3)、泛酸和辅酶A(CoA)生物合成(KEGG3)、近端小管碳酸氢盐回收(KEGG3)、半乳糖代谢(KEGG3)、淀粉和蔗糖代谢(KEGG3)、原发性免疫缺陷(KEGG3)、半胱氨酸和甲硫氨酸代谢(KEGG3)、泛醌和其他萜类醌生物合成(KEGG3)、DNA修复和重组蛋白(KEGG3)、酪氨酸代谢(KEGG3)、苯丙氨酸、酪氨酸和色氨酸生物合成(KEGG3)、氨酰-tRNA生物合成(KEGG3)、丙氨酸、天冬氨酸和谷氨酸代谢(KEGG3)、光合作用(KEGG3)、其他转运蛋白(KEGG3)、丁酸酯代谢(KEGG3)、细菌分泌系统(KEGG3)、甘油磷脂代谢(KEGG3)、氧化磷酸化(KEGG3)、I型糖尿病(KEGG3)、糖酵解/糖异生(KEGG3)、光合作用蛋白(KEGG3)、转运蛋白(KEGG3)、萜类骨架生物合成(KEGG3)、不饱和脂肪酸的生物合成(KEGG3)、信号转导机制(KEGG3)、酮体的合成和降解(KEGG3)、核苷酸切除修复(KEGG3)、分泌系统(KEGG3)、阿尔茨海默病(KEGG3)、玉米素生物合成(KEGG3)、II型糖尿病(KEGG3)、D-谷氨酰胺和D-谷氨酸代谢(KEGG3)、牛磺酸和亚牛磺酸代谢(KEGG3)、谷氨酸能突触(KEGG3)、植物-病原体相互作用(KEGG3)、维生素B6代谢(KEGG3)、柠檬酸循环(TCA循环)(KEGG3)、乙苯降解(KEGG3)、碱基切除修复(KEGG3)、复制、重组和修复蛋白(KEGG3)、真核生物的核糖体生物发生(KEGG3)、氨基苯甲酸酯降解(KEGG3)、细菌运动蛋白(KEGG3)、安莎霉素类的生物合成(KEGG3)、离子通道(KEGG3)、代谢(KEGG2)、表征欠佳(KEGG2)、次生代谢物的生物合成和生物降解(KEGG3)、硫辛酸代谢(KEGG3)、氨基酸有关酶(KEGG3)、转录蛋白(KEGG3)、抗坏血酸盐和藻酸盐代谢(KEGG3)、硫胺素代谢(KEGG3)、功能未知(KEGG3)、糖胺聚糖降解(KEGG3)、其他(KEGG3)、戊糖和葡萄糖醛酸酯相互转化(KEGG3)、生物素代谢(KEGG3)、苯丙氨酸代谢(KEGG3)、糖鞘脂生物合成-神经节系列(Glycosphingolipid biosynthesis-ganglio series)(KEGG3)、毛孔离子通道(KEGG3)、膜和细胞内结构分子(KEGG3)、嘌呤代谢(KEGG3)、叶酸一碳库(One carbon pool by folate)(KEGG3)、磷酸酯和次磷酸酯代谢(KEGG3)、溶酶体(KEGG3)、药物代谢-其他酶(KEGG3)、青霉素和头孢菌素生物合成(KEGG3)、亨廷顿病(Huntington's disease)(KEGG3)、烟酸盐和烟酰胺代谢(Nicotinate and nicotinamide metabolism)(KEGG3)、药物代谢-细胞色素P450(KEGG3)、脂多糖生物合成蛋白(KEGG3)、通过细胞色素P450的外源性物质代谢(KEGG3)、结核病(KEGG3)、多环芳烃降解(KEGG3)、和/或其他任何合适的功能特征(例如,如本文中描述的)。在变型中,用户的表征可以包括基于以对诊断和/或治疗的典型方法是附加的或可替代的方式监测以上特征的一种或多种,,将用户表征为具有一种或多种光敏性皮肤相关相关状况的人。Microbiome signatures associated with (e.g., positively correlated; negatively correlated; useful for diagnosis; etc.) one or more dry skin-related conditions (and/or other suitable skin-related conditions) can include signatures associated with (e.g., signatures describing their abundance; signatures describing their relative abundance; signatures describing functional aspects associated with them; signatures describing being derived from them; signatures describing their presence and/or absence; etc.) any combination of one or more of the following taxa: Corynebacteriaceae (family), Bacilli (class), Lactobacillales (order), Actinomycetes (order), Firmicutes (phylum), Corynebacterium (genus), Dermabacteraceae (family), Lactobacillaceae (family), (family), Propionibacteriaceae (family), Actinobacteria (class), Dermabacter (genus), Dialister (genus), Facklamia (genus), Lactobacillus (genus), Propionibacterium (genus), Corynebacterium (genus), Facklamia hominis (species), Corynebacterium species (species), Propionibacterium MSP09A species (species), Facklamia 1440-97 species (species), Staphylococcus C9I2 species (species), Anaerobic coccus 9402080 species (species), Corynebacterium glucuronolyticum (species), Dermabacterium hominis (species), hominis (species), Enterobacteriaceae (family), Pseudomonadaceae (family), Staphylococcaceae (family), Gammaproteobacteria (class), Bacillusales (order), Enterobacteriales (order), Bifidobacterium (genus), Pseudomonas (genus), Anaerococcus (genus), Kluyvera (genus), Atopobium (genus), Staphylococcus (genus), Lactobacillus BL302 (species), Corynebacterium mastitis (species), Bifidobacterium longum (species), Anaeroglobus geminatus (species), Anaerococcus S9 PR-16 species (species), Prevotella timoniensis (species), Kluyveromyces georginae (species), Actinomycetes (genus), Finegoldia (genus), Cronobacter (genus), Acinetobacter WB22-23 species (species), Anaerococcus octavius (species), Finegoldia S9 AA1-5 species (species), Staphylococcus C-D-MA2 species (species), Peptoniphilus 7-2 species (species), Cronobacter sakazakii (Cronobacter sakazakii (species), Pasteurellaceae (family), Acidobacteriia (class), Sphingobacteriia (class), Sphingobacteriales (order), Acidobacteria (phylum), Porphyromonas (genus), Haemophilus (genus), Acinetobacter (genus), Anaerobic cocci 8405254 species (species), Sphingomonadaceae (family) , Sphingomonadales (order), Kocuria (genus), Geminis (genus), Veillonella CM60 species (species), Lactobacillus 7_1_47FAA (species), Geminis 933-88 species (species), Porphyromonas cardiformis (species), Haemophilus parainfluenzae (species), Bacteroides AR20 species (species), Bacteroides vulgaris (species), Bacteroides D22 species (species), Dorea Longicatena (species), Parabacteroides faecalis (species), merdae (species), Bacteroides AR29 species (species), Dorea (genus), Collinsella (genus), Bacteroides (genus), Oscillospiraceae (family), Ruminococcaceae (family), Bacteroidetes (family), Verrucomicrobiaceae (family), Coriobacteriaceae (family), Clostridiales (order), Bacteroideales (order), Verrucomicrobiales (order), Coriobacteriales (order), Thermoanaerobacterales (order), Clostridia (class), Bacteroidetes (class), Verrucomicrobiae (class), Verrucomicrobia (phylum), Bacteroidetes (phylum), and/or other suitable taxa (e.g., as described herein); and/or may include any combination of one or more of the following: Related functional features (e.g., features describing its abundance; features describing its relative abundance; features describing functional aspects associated with it; features describing features derived from it; features describing its presence and/or absence; etc.): transcription (KEGG2), cellular processes and signaling (KEGG2), amino acid metabolism (KEGG2), cell growth and death (KEGG2), replication and repair (KEGG2), metabolism of other amino acids (KEGG2), neurodegenerative diseases (KEGG2), metabolism of cofactors and vitamins (KEGG2), transport and catabolism (KEGG2), KEGG2), endocrine system (KEGG2), immune system diseases (KEGG2), excretion system (KEGG2), enzyme family (KEGG2), membrane transport (KEGG2), carbohydrate metabolism (KEGG2), biosynthesis of other secondary metabolites (KEGG2), metabolism of terpenoids and polyketides (KEGG2), infectious diseases (KEGG2), genetic information processing (KEGG2), nervous system (KEGG2), environmental adaptation (KEGG2), nucleotide metabolism (KEGG2), signaling molecules and interactions (KEGG2), G2), signal transduction (KEGG2), transport and metabolism of inorganic ions (KEGG3), chromosomes (KEGG3), cell cycle – Caulobacter (KEGG3), ribosome biogenesis (KEGG3), DNA replication proteins (KEGG3), transcription factors (KEGG3), glycine, serine and threonine metabolism (KEGG3), sulfur metabolism (KEGG3), other ion-coupled transporters (KEGG3), biosynthesis of valine, leucine and isoleucine (KEGG3), nitrogen metabolism (KEGG3), peptidoglycan biosynthesis ( KEGG3), homologous recombination (KEGG3), peroxisomes (KEGG3), sulfur relay system (KEGG3), peptidases (KEGG3), protein kinases (KEGG3), mismatch repair (KEGG3), xylene degradation (KEGG3), ribosomes (KEGG3), RNA polymerase (KEGG3), tryptophan metabolism (KEGG3), histidine metabolism (KEGG3), vitamin metabolism (KEGG3), cell motility and secretion (KEGG3), pyrimidine metabolism (KEGG3), cytoskeletal proteins (KEGG3), DNA Reproduction (KEGG3), amino sugar and nucleotide sugar metabolism (KEGG3), folate biosynthesis (KEGG3), carbon fixation in photosynthetic organisms (KEGG3), phosphatidylinositol signaling system (KEGG3), lysine degradation (KEGG3), selenium compound metabolism (KEGG3), fructose and mannose metabolism (KEGG3), inositol phosphate metabolism (KEGG3), protein folding and related processing (KEGG3), proteasome proliferator-activated receptor (PPAR) signaling pathway (KEGG3), lipid metabolism (KEGG3), valine, leucine leucine and isoleucine degradation (KEGG3), glyoxylate and dicarboxylic acid metabolism (KEGG3), arginine and proline metabolism (KEGG3), limonene and pinene degradation (KEGG3), D-alanine metabolism (KEGG3), porphyrin and chlorophyll metabolism (KEGG3), C5-branched dicarboxylic acid metabolism (KEGG3), molecular chaperones and folding catalysts (KEGG3), fatty acid metabolism (KEGG3), glutathione metabolism (KEGG3), pentose phosphate pathway (KEGG3), phosphotransferase system (KEGG3), system,PTS)(KEGG3), pantothenate and coenzyme A (CoA) biosynthesis(KEGG3), proximal tubule bicarbonate recovery(KEGG3), galactose metabolism(KEGG3), starch and sucrose metabolism(KEGG3), primary immunodeficiency(KEGG3), cysteine and methionine metabolism(KEGG3), ubiquinone and other terpenoid quinone biosynthesis(KEGG3), DNA repair and recombination proteins(KEGG3), tyrosine metabolism(KEGG3), phenylalanine, tyrosine and tryptophan biosynthesis(KEGG3), aminoacyl-tRNA biosynthesis(KEGG3), alanine, aspartate and glutamate metabolism(KEGG3), photosynthesis (KEGG3), other transporters (KEGG3), butyrate metabolism (KEGG3), bacterial secretion system (KEGG3), glycerophospholipid metabolism (KEGG3), oxidative phosphorylation (KEGG3), type I diabetes (KEGG3), glycolysis/gluconeogenesis (KEGG3), photosynthesis proteins (KEGG3), transporters (KEGG3), terpenoid skeleton biosynthesis (KEGG3), unsaturated fatty acid biosynthesis (KEGG3), signal transduction mechanism (KEGG3), ketone body synthesis and degradation (KEGG3), nucleotide excision repair (KEGG3), secretion system (KEGG3), Alzheimer's disease (KEGG3), zeatin biosynthesis synthesis (KEGG3), type II diabetes (KEGG3), D-glutamine and D-glutamate metabolism (KEGG3), taurine and hypotaurine metabolism (KEGG3), glutamatergic synapses (KEGG3), plant-pathogen interactions (KEGG3), vitamin B6 metabolism (KEGG3), citric acid cycle (TCA cycle) (KEGG3), ethylbenzene degradation (KEGG3), base excision repair (KEGG3), replication, recombination and repair proteins (KEGG3), ribosome biogenesis in eukaryotes (KEGG3), aminobenzoate degradation (KEGG3), bacterial movement proteins (KEGG3), biosynthesis of ansamycins (KEGG3), Ion channels (KEGG3), metabolism (KEGG2), poorly characterized (KEGG2), biosynthesis and biodegradation of secondary metabolites (KEGG3), lipoic acid metabolism (KEGG3), amino acid-related enzymes (KEGG3), transcription proteins (KEGG3), ascorbate and alginate metabolism (KEGG3), thiamine metabolism (KEGG3), unknown function (KEGG3), glycosaminoglycan degradation (KEGG3), others (KEGG3), pentose and glucuronide interconversion (KEGG3), biotin metabolism (KEGG3), phenylalanine metabolism (KEGG3), glycosphingolipid biosynthesis-ganglionic series (KEGG3), biosynthesis-ganglio series)(KEGG3), pore ion channels(KEGG3), membrane and intracellular structural molecules(KEGG3), purine metabolism(KEGG3), one carbon pool by folate(KEGG3), phosphate and hypophosphite metabolism(KEGG3), lysosome(KEGG3), drug metabolism-other enzymes(KEGG3), penicillin and cephalosporin biosynthesis(KEGG3), Huntington's disease(KEGG3), Nicotinate and nicotinamide metabolism(KEGG3), drug metabolism-cytochrome P450(KEGG3), lipopolysaccharide biosynthesis proteins(KEGG3), xenobiotic metabolism by cytochrome P450(KEGG3), tuberculosis(KEGG3), polycyclic aromatic hydrocarbon degradation(KEGG3), and/or any other suitable functional features (e.g., as described herein). In variations, characterization of a user may include characterizing the user as a person having one or more photosensitive skin-related conditions based on monitoring one or more of the above characteristics in a manner additional to or alternative to typical methods of diagnosis and/or treatment.
在变型中,执行皮肤有关表征过程S135可以包括针对一种或多种头皮有关状况执行头皮有关状况表征过程。在一实施例中,皮肤有关表征过程可以基于统计分析,以识别具有与头皮有关状况最高关联性的特征集合,基于用衍生自受试者群体子集的训练数据集训练的、并用衍生自受试者群体子集的验证数据集进行验证的随机森林预测因子算法,一种或多种疗法对该头皮有关状况有积极作用。在实施例中,头皮有关状况可以包括诸如由皮肤干燥、刺激性油性皮肤、对护发产品的敏感性引起的头皮屑(例如,以剥落、瘙痒、头皮皮肤结垢为特征;等)和/或其他合适的头皮有关状况,可导致头皮微生物组失衡的其他状况和/或其他与头皮有关状况中的一种或多种。头皮有关状况可以与特定微生物群多样性和/或与肠道微生物的相对丰度有关的健康状况、与任何合适的生理位点相关联的微生物、微生物组功能多样性和/或其他合适的微生物组有关方面相关联。In a variation, performing the skin-related characterization process S135 may include performing a scalp-related condition characterization process for one or more scalp-related conditions. In one embodiment, the skin-related characterization process may be based on statistical analysis to identify a feature set with the highest correlation with a scalp-related condition, based on a random forest predictor algorithm trained with a training data set derived from a subset of the subject population and validated with a validation data set derived from a subset of the subject population, for which one or more therapies have a positive effect. In an embodiment, the scalp-related condition may include one or more of dandruff (e.g., characterized by flaking, itching, scaling of scalp skin, etc.) such as caused by dry skin, irritated oily skin, sensitivity to hair care products, and/or other suitable scalp-related conditions, other conditions that may lead to an imbalance in the scalp microbiome, and/or other scalp-related conditions. The scalp-related condition may be associated with a specific microbiome diversity and/or a health condition related to the relative abundance of intestinal microbes, microbes associated with any suitable physiological site, microbiome functional diversity, and/or other suitable microbiome-related aspects.
与一种或多种头皮有关状况(和/或其他合适的皮肤有关状况)相关联(例如,正相关;负相关;对诊断有用;等)的微生物组特征可以包括与以下分类群中的一种或多种的任意组合相关联的特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关的功能方面的特征;描述从其衍生的特征;描述其存在和/或不存在的特征;等):放线菌纲(纲)、乳杆菌目(目)、放线菌目(Actinomycetales)(目)、厚壁菌门(门)、皮杆菌科(科)、乳杆菌科(科)、丙酸杆菌科(科)、棒状杆菌科(科)、乳杆菌(属)、棒状杆菌属(属)、丙酸杆菌(属)、皮杆菌属(属)、另位球菌属(Eremococcus)(属)、弗莱堡棒状杆菌(Corynebacteriumfreiburgense)(种)、克里克拉另位球菌属(KEGG3)(Eremoc(KEGG3)occus coleocola)(种)、棒状杆菌种(种)、葡萄球菌C9I2种(种)、厌氧球菌8405254种(种)、解葡萄糖苷棒状杆菌(种)、人皮杆菌(种)、红蝽菌科(科)、肠杆菌科(科)、葡萄球菌科(科)、肠杆菌目(目)、芽孢杆菌目(目)、双歧杆菌属(属)、葡萄球菌属(Staphylococcus)(属)、阿托波菌属(属)、巨球菌(属)、乳腺炎棒状杆菌(种)、链球菌BS35a种(种)、大芬戈尔德菌(Finegoldia magna)(种)、金黄色葡萄球菌(Staphylococcus aureus)(种)、流感嗜血杆菌(Haemophilusinfluenza)(种)、棒状杆菌NML 97-0186种(种)、口腔分类单元链球菌G59种(种)、多拉菌属(属)、罗斯拜瑞菌11SE39种(种)、多拉长脂链霉素菌(种)、普雷沃菌科(科)、韦荣球菌科(Veillonellaceae)(科)、颤螺菌科(科)、革兰氏阴性菌纲(Negativicutes)、硒单胞菌目(Selenomonadales)(目)、芬戈尔德菌(属)、颤螺菌属(Oscillospira)(属)、肠道单胞菌属(Intestinimonas)(属)、弗雷范尔特菌属(Flavonifractor)(属)、普雷沃菌属(属)、莫亚拉菌属(Moryella)(属)、光冈链杆菌(Catenibacterium mitsuokai)(种)、产气柯林斯菌(Collinsella aerofaciens)(种)、嗜胨菌2002-2300004种(种)、犬棒状杆菌(Corynebacterium canis)(种)、芬戈尔德菌S9 AA1-5种(种)、口颊普雷沃菌(Prevotellabuccalis)(种)、浑浊戴阿利斯特杆菌(Dialister invisus)(种)、莫拉克斯菌属(Moraxella)(属)、奈瑟菌属(属)、粘液奈瑟菌(Neisseria mucosa)(种)、理研菌科(Rikenellaceae)(科)、和/或其他合适的分类群(例如,本文中所述);和/或可以包括与以下一项或多项的任何组合相关的功能特征(例如,描述其丰度的特征;描述其相对丰度的特征;描述与其相关的功能方面的特征;描述从其衍生的特征;描述其存在和/或不存在的特征;等):辅助因子和维生素的代谢(KEGG2)、酶家族(KEGG2)、脂质代谢(KEGG2)、免疫系统疾病(KEGG2)、糖酵解/糖异生(KEGG3)、原发性免疫缺陷(KEGG3)、丙酮酸盐代谢(KEGG3)、运输和分解代谢(KEGG2)、神经退行性疾病(KEGG2)、内分泌系统(KEGG2)、氨基酸代谢(KEGG2)、细胞过程和信号传导(KEGG2)、信号分子与相互作用(KEGG2)、其他氨基酸的代谢(KEGG2)、复制和修复(KEGG2)、转录(KEGG2)、细胞生长和死亡(KEGG2)、膜运输(KEGG2)、其他次生代谢产物的生物合成(KEGG2)、萜类化合物和聚酮化合物的代谢(KEGG2)、无机离子的运输与代谢(KEGG3)、维生素代谢(KEGG3)、缬氨酸、亮氨酸和异亮氨酸的生物合成(KEGG3)、过氧化物酶体(KEGG3)、核糖体生物发生(KEGG3)、硒化合物代谢(KEGG3)、组氨酸代谢(KEGG3)、染色体(KEGG3)、硫代谢(KEGG3)、PPAR信号传导通路(KEGG3)、卟啉和叶绿素代谢(KEGG3)、磷脂酰肌醇信号传导系统(KEGG3)、肌醇磷酸代谢(KEGG3)、硫中继系统(KEGG3)、甘氨酸、丝氨酸和苏氨酸代谢(KEGG3)、DNA复制蛋白(KEGG3)、泛酸和CoA生物合成(KEGG3)、转录因子(KEGG3)、蛋白质折叠和相关处理(KEGG3)、II型糖尿病(KEGG3)、蛋白激酶(KEGG3)、叶酸生物合成(KEGG3)、赖氨酸降解(KEGG3)、RNA聚合酶(KEGG3)、D-丙氨酸代谢(KEGG3)、光合生物中的碳固定(KEGG3)、氮代谢(KEGG3)、甘油磷脂代谢(KEGG3)、安莎霉素类的生物合成(KEGG3)、缬氨酸、亮氨酸和异亮氨酸降解(KEGG3)、细胞骨架蛋白(KEGG3)、肽酶(KEGG3)、脂肪酸代谢(KEGG3)、细胞循环-柄杆菌属(KEGG3)、磷酸转移酶系统(PTS)(KEGG3)、嘧啶代谢(KEGG3)、阿尔茨海默病(KEGG3)、丁酸酯代谢(KEGG3)、色氨酸代谢(KEGG3)、信号转导机制(KEGG3)、磷酸戊糖途径(KEGG3)、其他离子耦合的转运蛋白(KEGG3)、同源重组(KEGG3)、复制、重组和修复蛋白(KEGG3)、二甲苯降解(KEGG3)、错配修复(KEGG3)、乙醛酸和二羧酸代谢(KEGG3)、精氨酸和脯氨酸代谢(KEGG3)、肽聚糖的生物合成(KEGG3)、分子伴侣和折叠催化物(KEGG3)、I型糖尿病(KEGG3)、DNA复制(KEGG3)、细菌分泌系统(KEGG3)、酪氨酸代谢(KEGG3)、柠檬酸循环(TCA循环)(KEGG3)、氨基糖和核苷酸糖代谢(KEGG3)、核糖体(KEGG3)、柠檬烯和蒎烯降解(KEGG3)、细胞运动和分泌(KEGG3)、牛磺酸和亚牛磺酸代谢(KEGG3)、氧化磷酸化(KEGG3)、果糖和甘露糖代谢(KEGG3)、维生素B6代谢(KEGG3)、离子通道(KEGG3)、酮体的合成和降解(KEGG3)、其他转运蛋白(KEGG3)、半乳糖代谢(KEGG3)、多环芳烃降解(KEGG3)、转运蛋白(KEGG3)、DNA修复和重组蛋白(KEGG3)、淀粉和蔗糖代谢(KEGG3)、丙氨酸、天冬氨酸和谷氨酸代谢(KEGG3)、真核生物的核糖体生物发生(KEGG3)、分泌系统(KEGG3)、不饱和脂肪酸的生物合成(KEGG3)、半胱氨酸和甲硫氨酸代谢(KEGG3)、碱基切除修复(KEGG3)、氨基苯甲酸酯降解(KEGG3)、光合作用(KEGG3)、光合作用蛋白(KEGG3)、毛孔离子通道(KEGG3)、脂质生物合成蛋白(KEGG3)、D-谷氨酰胺和D-谷氨酸代谢(KEGG3)、和/或任何其他合适的功能特征(例如,本文中所述等)。在变型中,用户的表征可以包括基于以对诊断和/或治疗的典型方法是附加的或可替代的方式检测以上特征的一种或多种,将用户表征为具有一种或多种光敏性皮肤相关状况的人。Microbiome signatures associated with (e.g., positively correlated; negatively correlated; useful for diagnosis; etc.) one or more scalp-related conditions (and/or other suitable skin-related conditions) can include signatures associated with any combination of one or more of the following taxa (e.g., signatures describing their abundance; signatures describing their relative abundance; signatures describing functional aspects associated with them; signatures describing derivations from them; signatures describing their presence and/or absence; etc.): Actinomycetes (class), Lactobacilliales (order), Actinomycetales (order), Firmicutes (phylum), Dermobacteriaceae (family), Lactobacillaceae (family), Propionibacteriumaceae (family), Corynebacterium (genus), Corynebacterium (genus), Propionibacterium (genus), Dermobacterium (genus), Eremococcus (genus), Corynebacterium freiburgense (species), Eremococcus kriklagensis (KEGG3) (KEGG4) (KEGG5) coleocola)(species), Corynebacterium species(species), Staphylococcus C9I2 species(species), Anaerobic cocci 8405254 species(species), Corynebacterium glucosides (species), Dermatobacterium hominis (species), Rhodomycetaceae(family), Enterobacteriaceae(family), Staphylococcaceae(family), Enterobacteriales(order), Bacillusales(order), Bifidobacterium(genus), Staphylococcus(genus), Atopobium(genus), Megasphaera(genus), Corynebacterium mastitis(species), Streptococcus BS35a species(species), Finegoldia magna(species), Staphylococcus aureus(species), Haemophilus influenzae(species), Corynebacterium NML 97-0186 species (species), oral taxa Streptococcus G59 species (species), Dora (genus), Rosebair 11SE39 species (species), Dora Lipostreptococcus (species), Prevotella (family), Veillonellaceae (family), Oscillospiraceae (family), Gram-negative bacteria (Negativicutes), Selenomonasales (order), Fingoldia (genus), Oscillospira (genus), Intestinimonas (genus), Flavonifractor (genus), Prevotella (genus), Moryella (genus), Catenibacterium mitsuokai (species), Collinsella aerogenes (genus), aerofaciens (species), Peptophilus 2002-2300004 (species), Corynebacterium canis (species), Fingoldella S9 AA1-5 (species), Prevotellabuccalis (species), Dialister invisus (species), Moraxella (genus), Neisseria (genus), Neisseria mucosa (species), mucosa (species), Rikenellaceae (family), and/or other suitable taxonomic groups (e.g., as described herein); and/or may include functional features (e.g., features describing its abundance; features describing its relative abundance; features describing functional aspects associated with it; features describing its derivation from it; features describing its presence and/or absence; etc.) associated with any combination of one or more of the following: metabolism of cofactors and vitamins (KEGG2), enzyme families (KEGG2), lipid metabolism (KEGG2), immune system diseases (KEGG2), glycolysis/gluconeogenesis (KEGG2), G3), primary immune deficiency (KEGG3), pyruvate metabolism (KEGG3), transport and catabolism (KEGG2), neurodegenerative diseases (KEGG2), endocrine system (KEGG2), amino acid metabolism (KEGG2), cellular processes and signaling (KEGG2), signaling molecules and interactions (KEGG2), metabolism of other amino acids (KEGG2), replication and repair (KEGG2), transcription (KEGG2), cell growth and death (KEGG2), membrane transport (KEGG2), biosynthesis of other secondary metabolites (KEGG2), terpenoids and polyketide Metabolism of compounds (KEGG2), transport and metabolism of inorganic ions (KEGG3), vitamin metabolism (KEGG3), biosynthesis of valine, leucine and isoleucine (KEGG3), peroxisomes (KEGG3), ribosome biogenesis (KEGG3), selenium compound metabolism (KEGG3), histidine metabolism (KEGG3), chromosomes (KEGG3), sulfur metabolism (KEGG3), PPAR signaling pathway (KEGG3), porphyrin and chlorophyll metabolism (KEGG3), phosphatidylinositol signaling system (KEGG3), inositol phosphate metabolism (KEGG3), sulfur relay system (KEGG3), glycine, serine and threonine metabolism (KEGG3), DNA replication proteins (KEGG3), pantothenate and CoA biosynthesis (KEGG3), transcription factors (KEGG3), protein folding and related processing (KEGG3), type II diabetes (KEGG3), protein kinases (KEGG3), folate biosynthesis (KEGG3), lysine degradation (KEGG3), RNA polymerase (KEGG3), D-alanine metabolism (KEGG3), carbon fixation in photosynthetic organisms (KEGG3), nitrogen metabolism (KEGG3), glycerophospholipid metabolism (KEGG3), Biosynthesis of ansamycins (KEGG3), Valine, Leucine and Isoleucine degradation (KEGG3), Cytoskeletal proteins (KEGG3), Peptidases (KEGG3), Fatty acid metabolism (KEGG3), Cell cycle - Caulobacter (KEGG3), Phosphotransferase system (PTS) (KEGG3), Pyrimidine metabolism (KEGG3), Alzheimer's disease (KEGG3), Butyrate metabolism (KEGG3), Tryptophan metabolism (KEGG3), Signal transduction mechanisms (KEGG3), Pentose phosphate pathway (KEGG3), Other ion-coupled transporters (KEGG3), Homologous recombination (KEGG3), replication, recombination and repair proteins (KEGG3), dimethylbenzene degradation (KEGG3), mismatch repair (KEGG3), glyoxylate and dicarboxylic acid metabolism (KEGG3), arginine and proline metabolism (KEGG3), peptidoglycan biosynthesis (KEGG3), molecular chaperones and folding catalysts (KEGG3), type I diabetes (KEGG3), DNA replication (KEGG3), bacterial secretion system (KEGG3), tyrosine metabolism (KEGG3), citric acid cycle (TCA cycle) (KEGG3), amino sugar and nucleotide sugar metabolism (KEGG3), ribosome (KEGG 3), limonene and pinene degradation (KEGG3), cell motility and secretion (KEGG3), taurine and hypotaurine metabolism (KEGG3), oxidative phosphorylation (KEGG3), fructose and mannose metabolism (KEGG3), vitamin B6 metabolism (KEGG3), ion channels (KEGG3), ketone body synthesis and degradation (KEGG3), other transporters (KEGG3), galactose metabolism (KEGG3), polycyclic aromatic hydrocarbons degradation (KEGG3), transporters (KEGG3), DNA repair and recombination proteins (KEGG3), starch and sucrose metabolism (KEGG3), alanine, aspartate and glutamate metabolism (KEGG3), ribosome biogenesis in eukaryotes (KEGG3), secretion system (KEGG3), biosynthesis of unsaturated fatty acids (KEGG3), cysteine and methionine metabolism (KEGG3), base excision repair (KEGG3), aminobenzoate degradation (KEGG3), photosynthesis (KEGG3), photosynthesis proteins (KEGG3), pore ion channels (KEGG3), lipid biosynthesis proteins (KEGG3), D-glutamine and D-glutamate metabolism (KEGG3), and/or any other suitable functional feature (e.g., as described herein, etc.). In a variation, characterization of a user can include characterizing the user as a person with one or more photosensitive skin-related conditions based on detecting one or more of the above features in a manner that is additional or alternative to typical methods of diagnosis and/or treatment.
然而,确定一种或多种皮肤有关表征可以以任何合适的方式来执行。However, determining one or more skin-related characteristics may be performed in any suitable manner.
4.4确定疗法模型4.4 Determine the treatment model
方法100可以附加地或可替代地包括框S140,框S140可以包括生成配置成调节根据表征过程表征的受试者中微生物分布的疗法模型。框S140可以起到以下作用:识别、排序、优先考虑(prioritize)、确定、预测、劝阻和/或以其他方式促进对疗法(例如,基于益生菌的疗法、基于噬菌体的疗法、基于小分子的疗法等)的疗法确定,诸如可以使受试者的微生物组组成和/或功能特征(例如,针对任何合适位点的微生物组,等)朝着在推广受试者健康中所期望的平衡状态转变的疗法;和/或确定用于以其他方式修改一种或多种微生物有关状况的状态的疗法(例如,修改与人类行为状况相关的用户行为,等)。微生物有关状况模型可包括一种或多种疗法模型。在框S140中,疗法可以从包括以下一种或多种的疗法中选择:益生菌疗法、基于噬菌体的疗法、基于小分子的疗法、认知/行为疗法、物理康复疗法、临床疗法、基于药物的疗法、饮食有关疗法、和/或旨在以任何其他合适的方式操作以推广用户健康的任何其他合适疗法。在基于细菌噬菌体的疗法的特定实施例中,对受试者中所代表的某些细菌(或其他微生物)特异的细菌噬菌体的一个或多个群体(例如,以菌落形成单元来表示)可用于下调或以其他方式消除某些细菌的群体。这样,基于细菌噬菌体的疗法可用于减少受试者中所代表的细菌的不期望群体的大小。作为补充,基于细菌噬菌体的疗法可用于增加未被所用细菌噬菌体靶向的细菌群体的相对丰度。Method 100 may additionally or alternatively include block S140, which may include generating a therapy model configured to adjust the distribution of microorganisms in a subject characterized according to the characterization process. Block S140 may serve the following functions: identifying, sorting, prioritizing, determining, predicting, discouraging and/or otherwise promoting therapy determinations for therapies (e.g., probiotic-based therapies, phage-based therapies, small molecule-based therapies, etc.), such as therapies that can shift the composition and/or functional characteristics of the subject's microbiome (e.g., microbiome for any suitable site, etc.) toward a desired state of balance in promoting the health of the subject; and/or determining therapies for otherwise modifying the state of one or more microbial-related conditions (e.g., modifying user behavior associated with human behavior conditions, etc.). The microbial-related condition model may include one or more therapy models. In box S140, the therapy can be selected from the following therapies including one or more: probiotic therapy, phage-based therapy, small molecule-based therapy, cognitive/behavioral therapy, physical rehabilitation therapy, clinical therapy, drug-based therapy, diet-related therapy, and/or any other suitable therapy designed to operate in any other suitable manner to promote the health of the user. In a specific embodiment of a bacteriophage-based therapy, one or more populations of bacteriophages (e.g., expressed in colony forming units) specific to certain bacteria (or other microorganisms) represented in the subject can be used to downregulate or otherwise eliminate certain bacterial populations. In this way, bacteriophage-based therapy can be used to reduce the size of an undesirable population of bacteria represented in the subject. In addition, bacteriophage-based therapy can be used to increase the relative abundance of bacterial populations that are not targeted by the bacteriophage used.
在益生菌疗法的另一个特定实施例中,如图4所示,该疗法模型的候选疗法可以执行以下一项或多项:通过提供物理屏障(例如,通过定植抗性的方式)阻止病原体进入上皮细胞、通过刺激杯状细胞(goblet cell)诱导粘液性屏障的形成、(例如,通过刺激闭合小环1(zona-occludens 1)的上调、通过阻止紧密连接蛋白(tight junction protein)再分布)增强受试者的上皮细胞之间顶端紧密连接的完整性、产生抗微生物因子、(例如,通过树突细胞的信号传导和调节T细胞的诱导)刺激抗炎性细胞因子的产生、触发免疫反应、以及执行将受试者的微生物组从失调状态中调整出去的任何其他合适功能。在另一个特定实施例中,疗法可以包括基于医疗设备的疗法(例如,与人类行为修改相关联的、与疾病有关状况的治疗相关联的、等)。In another specific embodiment of probiotic therapy, as shown in FIG4 , the candidate therapy of the therapy model can perform one or more of the following: prevent pathogens from entering epithelial cells by providing a physical barrier (e.g., by means of colonization resistance), induce the formation of a mucous barrier by stimulating goblet cells, enhance the integrity of apical tight junctions between epithelial cells of the subject (e.g., by stimulating upregulation of zona-occludens 1, by preventing redistribution of tight junction proteins), produce antimicrobial factors, stimulate the production of anti-inflammatory cytokines (e.g., through signaling of dendritic cells and induction of regulatory T cells), trigger an immune response, and perform any other suitable function to adjust the subject's microbiome out of a dysregulated state. In another specific embodiment, the therapy can include a medical device-based therapy (e.g., associated with human behavior modification, associated with the treatment of disease-related conditions, etc.).
在变型中,疗法模型优选地基于来自大的受试者群体的数据,其可以包括在框S110中从其衍生出微生物组多样性数据集的受试者群体,其中良好地表征了充分暴露于各种治疗措施之前和之后的微生物组组成和/或功能特征或健康状态。这些数据可用于在识别治疗措施中训练和验证疗法提供模型,该治疗措施基于不同的微生物有关表征为受试者提供期望结果。在变型中,作为有监督的机器学习算法,支持向量机(support vectormachine)可以用于生成疗法提供模型。然而,上述任何其他合适的机器学习算法都可以促进疗法提供模型的生成。In a variation, the therapy model is preferably based on data from a large subject population, which can be included in a subject population from which a microbiome diversity data set is derived in frame S110, wherein the microbiome composition and/or functional characteristics or health status before and after being fully exposed to various treatment measures are well characterized. These data can be used to train and verify the therapy in identifying treatment measures to provide a model, and the treatment measures provide the desired results for the subject based on different microorganisms. In a variation, as a supervised machine learning algorithm, a support vector machine can be used to generate a therapy to provide a model. However, any other suitable machine learning algorithm mentioned above can promote the generation of the therapy to provide a model.
附加地或可替代地,疗法模型可关于从被识别为身体健康的受试者群体的受试者评估的“正常”或基线微生物组组成和/或功能特征的识别而衍生。根据表征为身体健康的受试者群体的受试者子集的识别(例如,使用表征过程的特征),在框S140中可以生成朝着身体健康受试者的微生物组组成和/或功能特征调节微生物组组成和/或功能特征的疗法。框S140因此可包括识别一种或多种基线微生物组组成和/或功能特征(例如,针对人口统计学集合的每一个的一个基线微生物组)、以及可使处于生态失调状态的受试者的微生物组朝着所识别的基线微生物组组成和/或功能特征之一转换的潜在治疗剂型和治疗方案。然而,疗法模型可以以任何合适的方式生成和/或完善。Additionally or alternatively, the therapy model may be derived from the identification of a "normal" or baseline microbiome composition and/or functional characteristics assessed from a subject population identified as being physically healthy. Based on the identification of a subset of subjects characterized as being physically healthy (e.g., using features of a characterization process), a therapy that modulates the microbiome composition and/or functional characteristics toward the microbiome composition and/or functional characteristics of physically healthy subjects may be generated in block S140. Block S140 may therefore include identifying one or more baseline microbiome compositions and/or functional characteristics (e.g., one baseline microbiome for each of a demographic set), and potential therapeutic formulations and treatment regimens that may convert the microbiome of a subject in a dysbiotic state toward one of the identified baseline microbiome compositions and/or functional characteristics. However, the therapy model may be generated and/or improved in any suitable manner.
与同疗法模型相关联的益生菌疗法相关联的微生物组成优选包括微生物,该微生物是可培养的(例如,能够被扩展以提供可扩展(scalable)疗法)且非致死性的(例如,在它们期望的治疗剂量中是非致死性的)。此外,微生物组成可包括单一类型微生物,该单一类型微生物对受试者的微生物组具有急性作用或中度作用。附加地或可替代地,微生物组成可以包括多种类型微生物的平衡组合,该多种类型微生物的平衡组合配置为在朝着期望状态驱动受试者微生物组中彼此协作。例如,益生菌疗法中多种类型细菌的组合可以包括第一细菌类型,第一细菌类型生成被第二细菌类型使用的产物,第二细菌类型在积极影响受试者的微生物组中具有强作用。附加地或可替代地,在益生菌疗法中多种类型细菌的组合可以包括产生具有相同功能的蛋白质的几种细菌类型,该具有相同功能的蛋白质积极影响受试者微生物组。The microbial composition associated with the probiotic therapy associated with the allopathic model preferably includes microorganisms that are culturable (e.g., able to be expanded to provide scalable therapy) and non-lethal (e.g., non-lethal in their desired therapeutic dose). In addition, the microbial composition may include a single type of microorganism that has an acute effect or a moderate effect on the subject's microbiome. Additionally or alternatively, the microbial composition may include a balanced combination of multiple types of microorganisms that are configured to cooperate with each other in driving the subject's microbiome toward a desired state. For example, a combination of multiple types of bacteria in a probiotic therapy may include a first bacterial type that generates a product used by a second bacterial type, and the second bacterial type has a strong effect in actively affecting the subject's microbiome. Additionally or alternatively, a combination of multiple types of bacteria in a probiotic therapy may include several bacterial types that produce proteins with the same function, which positively affect the subject's microbiome.
益生菌组成可以天然衍生或合成衍生。例如,在一种应用中,益生菌组成可以天然衍生自(例如,如使用表征过程和疗法模型识别的,具有基线微生物组组成和/或功能特征的一个或多个受试者的)粪便物或其他生物物质。附加地或可替代地,如使用表征过程和治疗模型所识别的,益生菌组成可以基于基线微生物组组成和/或功能特征,来人工合成地衍生(例如,使用台式(benchtop)方法衍生)。在变型中,可用于益生菌疗法的微生物剂可包括以下一种或多种:酵母菌(例如,布拉迪酵母菌(Saccharomyces boulardii))、革兰氏阴性菌(例如,尼斯勒大肠杆菌(E.coli Nissle))、革兰氏阳性菌(例如,重组双歧杆菌(Bifidobacteria bifidum)、婴儿双歧杆菌(Bifidobacteria infantis)、鼠李糖乳杆菌(Lactobacillus rhamnosus)、乳酸乳球菌(Lactococcus lactis)、植物乳杆菌(Lactobacillus plantarum)、嗜酸乳杆菌(Lactobacillus acidophilus)、干酪乳杆菌(Lactobacillus casei)、多发酵芽孢杆菌(Bacillus polyfermenticus)等),以及任何其他合适类型的微生物剂。The probiotic composition can be naturally derived or synthetically derived. For example, in one application, the probiotic composition can be naturally derived from fecal matter or other biological matter (e.g., from one or more subjects with a baseline microbiome composition and/or functional characteristics as identified using the characterization process and therapy model). Additionally or alternatively, the probiotic composition can be synthetically derived (e.g., derived using a benchtop method) based on the baseline microbiome composition and/or functional characteristics as identified using the characterization process and therapy model. In variations, microbial agents useful in probiotic therapy may include one or more of yeast (e.g., Saccharomyces boulardii), Gram-negative bacteria (e.g., E. coli Nissle), Gram-positive bacteria (e.g., Bifidobacteria bifidum, Bifidobacteria infantis, Lactobacillus rhamnosus, Lactococcus lactis, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus casei, Bacillus polyfermenticus, etc.), and any other suitable type of microbial agent.
在一变型中,疗法可以包括针对一种或多种皮肤有关状况的益生菌疗法(例如,用于改进与一种或多种皮肤有关状况相关联的健康状态;等),其中益生菌疗法可以包括以下任何一项或多项的组合:溃疡棒状杆菌、人费克蓝姆菌、棒状杆菌种、丙酸杆菌MSP09A种、费克蓝姆菌1440-97种、葡萄球菌C9I2种、厌氧球菌9402080种、解葡萄糖苷棒状杆菌、人皮杆菌、乳杆菌BL302种、乳腺炎棒状杆菌、长双歧杆菌、双子厌氧球菌、厌氧球菌S9 PR-16种、蒂莫宁普雷沃菌、乔治亚娜克鲁维菌、不动杆菌WB22-23种、八叠厌氧球菌、芬戈尔德菌S9AA1-5种、葡萄球菌C-D-MA2种、嗜胨菌7-2种、阪崎克罗诺杆菌、厌氧球菌8405254种、韦荣球菌CM60种、乳杆菌7_1_47FAA种、孪生球菌933-88种、卡式卟啉单胞菌、副流感嗜血杆菌、拟杆菌AR20种、普通拟杆菌、拟杆菌D22种、多拉长脂链霉素菌、粪副拟杆菌、拟杆菌AR29种、普雷沃菌WAL 2039G种、普拉栖粪杆菌、粪布劳特菌、腐败另枝菌、产酸拟杆菌、产液阿德勒克罗伊茨菌、琥珀酸考拉杆菌、食葡糖罗斯拜瑞菌、考拉杆菌377种、匹格脱硫弧菌、埃格特菌HGA1种、内脂因子长形乳杆菌、另枝菌HGB5种、丝状霍尔德曼氏菌、肠道柯林斯菌、猕猴奈瑟菌(Neisseria macacae)、血孪生球菌、脆弱拟杆菌、口普雷沃菌、布伦纳假单胞菌、鲸黄杆菌、短波单胞菌FXJ8.080种、普列比乌斯拟杆菌、寒武小弯杆菌、韦克斯勒布劳特菌、葡萄球菌WB18-16种、口腔分类单元链球菌G63种、疮疱丙酸杆菌、厌氧球菌9401487种、表皮葡萄球菌、解脲弯曲杆菌、两面神菌M3-5种、嗜胨菌DNF00840种、芬戈尔德菌S8 F7种、解糖胨普雷沃菌、牙周梭杆菌、弗莱堡棒状杆菌、克里克拉另位球菌、链球菌BS35a种、大芬戈尔德菌、金黄色葡萄球菌、流感嗜血杆菌、棒状杆菌NML 97-0186种、口腔分类单元链球菌G59种、罗斯拜瑞菌11SE39种、光冈链杆菌、产气柯林斯菌、嗜胨菌2002-2300004种、犬棒状杆菌、口颊普雷沃菌、浑浊戴阿利斯特杆菌、粘液奈瑟菌、和/或任何合适的分类群(例如,本文中描述的)和/或噬菌体向量(例如,细菌噬菌体、病毒等)的任何其他合适微生物。在一特定实施例中,益生菌疗法和/或其他合适的益生菌疗法可以以10万至100亿个菌落形成单位(colony-forming unit,CFU)的剂量推广(例如,建议;以其他方式提供;等),如从预测响应于疗法患者微生物组的正向调整的疗法模型中所确定的。在实施例中,可以根据为他/她的以下一项或多项定制的方案指示受试者摄食包含益生菌制剂的胶囊剂:生理学(例如,体重指数、体重、身高)、人口统计学(例如,性别、年龄)、生态失调的严重程度、对药物的敏感性和/或任何其他合适的因素。In one variation, the therapy may include a probiotic therapy for one or more skin-related conditions (e.g., for improving a health state associated with one or more skin-related conditions; etc.), wherein the probiotic therapy may include any one or more of the following in combination: Corynebacterium ulcerans, Fecklumella hominis, Corynebacterium species, Propionibacterium species MSP09A, Fecklumella species 1440-97, Staphylococcus aureus C9I2, Anaerobic cocci species 9402080, Corynebacterium glucosinolates, Bacillus hominis, Lactobacillus species BL302, Corynebacterium mastitis, Bifidobacterium longum, Anaerobic cocci species, Anaerobic cocci species S9 PR-16, Prevotella timoniensis, Kluyveromyces georginae, Acinetobacter WB22-23, Anaerobic cocci of octaci, Fingoldella S9AA1-5, Staphylococcus C-D-MA2, Peptophilus 7-2, Cronobacter sakazakii, Anaerobic cocci 8405254, Veillonella CM60, Lactobacillus 7_1_47FAA, Gemini 933-88, Porphyromonas cardiogensis, Haemophilus parainfluenzae, Bacteroides AR20, Bacteroides vulgaris, Bacteroides D22, Streptococcus dorae, Parabacteroides faecalis, Bacteroides AR29, Prevotella WAL 2039G, Faecalibacterium prausnitzii, Blautus fecal, Bacteroides putrefaciens, Bacteroides acidophilus, Adler Kreutz, Pseudomonas succinici, Roseborgia glucosphaeria, Pseudomonas 377, Desulfovibrio pilosulatus, Eggertella HGA1, Lactobacillus longum, Bacteroides HGB5, Holdermanella filamentosa, Collinsella enterica, Neisseria macaques (Neisseria macacae), Geminis, Bacteroides fragilis, Prevotella oralis, Pseudomonas brenner, Flavobacterium ceti, Brevundimonas FXJ8.080, Bacteroides plebius, Curvularia cambriana, Wexlera, Staphylococcus WB18-16, Oral taxa Streptococcus G63, Propionibacterium acnes, Anaerobic cocci 9401487, Staphylococcus epidermidis, Campylobacter urealyticum, Janus M3-5, Peptophilus DNF00840, Fingoldiella S8 F7, Prevotella saccharolyticus, Fusobacterium periodontalis, Corynebacterium freiburgii, Krickla, Streptococcus BS35a, Fingoldiella major, Staphylococcus aureus, Haemophilus influenzae, Corynebacterium NML 97-0186, oral taxon Streptococcus G59, Roseborgia 11SE39, Streptobacillus mitsuoka, Collinsella aerogenes, Peptophilus 2002-2300004, Corynebacterium canis, Prevotella oralis, Dialisterella opacus, Neisseria mucoides, and/or any other suitable microorganism of any suitable taxonomic group (e.g., described herein) and/or phage vector (e.g., bacteriophage, virus, etc.). In a specific embodiment, the probiotic therapy and/or other suitable probiotic therapy can be promoted (e.g., recommended; otherwise provided; etc.) at a dose of 100,000 to 10 billion colony-forming units (CFU), as determined from a therapy model that predicts a positive adjustment of the patient's microbiome in response to therapy. In embodiments, a subject may be instructed to ingest capsules comprising a probiotic formulation according to a regimen customized for one or more of his/her physiology (e.g., body mass index, weight, height), demographics (e.g., sex, age), severity of dysbiosis, sensitivity to medications, and/or any other suitable factors.
在一变型中,对于表现出一种或多种皮肤有关状况的受试者,所述皮肤有关状况包括一种或多种光敏性相关状况、皮肤干燥相关状况、头皮相关状况和/或其他合适的皮肤有关状况,与皮肤有关状况相关的微生物可以基于存在于受试者微生物组中的微生物中相对丰度可识别模式的组成或多样性提供数据集,并且该与皮肤有关状况相关的微生物可以用作使用生物信息学管道(bioinformatics pipelines)和/或以上描述的表征的诊断工具和/或治疗工具。In one variation, for a subject exhibiting one or more skin-related conditions, including one or more photosensitivity-related conditions, dry skin-related conditions, scalp-related conditions, and/or other suitable skin-related conditions, microorganisms associated with the skin-related conditions can provide a dataset based on the composition or diversity of recognizable patterns of relative abundance among the microorganisms present in the subject's microbiome, and the microorganisms associated with the skin-related conditions can be used as a diagnostic tool and/or a therapeutic tool using the bioinformatics pipelines and/or characterizations described above.
在另一变型中,微生物数据集(例如,基于存在于受试者微生物组中的微生物中相对丰度可识别模式的组成或多样性)可以用作使用生物信息学管道和以上描述的表征的诊断工具。然而,益生菌疗法和/或其他合适的疗法可以包括与本文中所述的任何合适的分类群相关的微生物的任何合适组合。In another variation, a microbial dataset (e.g., composition or diversity based on patterns of relative abundance identifiable in the microorganisms present in a subject's microbiome) can be used as a diagnostic tool using a bioinformatics pipeline and the characterization described above. However, probiotic therapy and/or other suitable therapies can include any suitable combination of microorganisms associated with any suitable taxonomic group described herein.
益生菌和/或其他合适的消耗品可以以10万至100亿个CFU的剂量(和/或其他合适的剂量)提供,例如从预测响应于疗法的患者微生物组积极调整的疗法模型中所确定的。在一特定实施例中,可以根据为他/她的以下一项或多项定制的方案指示受试者摄入包含益生菌制剂的胶囊:生理学(例如,体重指数、体重、身高)、人口统计学(例如,性别、年龄)、生态失调的严重程度、对药物的敏感性和/或任何其他合适的因素。对于表现出微生物有关状况的受试者,相关联微生物(例如,对应于关联微生物组组成特征)可以基于存在于受试者微生物组中的微生物中相对丰度可识别模式的组成或多样性提供数据集,并且可以用作使用生物信息学管道和以上描述的表征的诊断工具。Probiotics and/or other suitable consumables can be provided at a dose of 100,000 to 10 billion CFU (and/or other suitable doses), for example as determined from a therapy model that predicts a positive adjustment of a patient's microbiome in response to therapy. In a particular embodiment, a subject can be instructed to ingest a capsule containing a probiotic formulation according to a regimen customized for one or more of his/her: physiology (e.g., body mass index, weight, height), demographics (e.g., sex, age), severity of dysbiosis, sensitivity to drugs, and/or any other suitable factors. For subjects exhibiting microbial-related conditions, associated microorganisms (e.g., corresponding to associated microbiome composition features) can provide a dataset based on the composition or diversity of recognizable patterns of relative abundance in microorganisms present in the subject's microbiome, and can be used as a diagnostic tool using a bioinformatics pipeline and the characterization described above.
4.5处理用户生物样品4.5 Processing of User Biological Samples
方法100可以附加地或可替代地包括框S150,框S150可以包括处理来自用户的一个或多个生物样品(例如,来自用户的不同收集位点的生物样品,等)。框S150可以起到促进受试者的微生物数据集的生成的作用,例如在衍生用于表征过程的输入(例如,用于诸如通过应用一个或多个微生物组表征模块针对用户生成微生物有关表征,等)中使用。这样,框S150可以包括从一个或多个用户接收、处理和/或分析一个或多个生物样品(例如,针对同一用户随时间变化的多个生物样品、针对不同用户的不同生物样品,等)。在框S150中,生物样品优选以非侵入性方式从受试者和/或受试者的环境生成。在变型中,样品接收的非侵入性方式可以使用以下任何一项或多项:可渗透的基底(例如,配置为擦拭受试者的身体区域的拭子(swab)、卫生纸、海绵等)、不可渗透的基底(例如,载玻片(slide)、胶带等)、配置为接收来自受试者身体区域的样品的容器(例如,药瓶、试管、袋子等)、以及任何其他合适的样品接收元件。在一特定实施例中,可以以非侵入性方式(例如,使用拭子和药瓶)从受试者的鼻、皮肤、生殖器、口和肠中的一个或多个收集生物样品。然而,生物样品可以附加地或可替代地以半侵入性方式或侵入性方式接收。在变型中,样品接收的侵入性方式可以使用以下任何一项或多项:针、注射器、活检元件、刺血针、以及用于以半侵入性或侵入性方式收集样品的任何其他合适的仪器。在特定实施例中,样品可以包括血液样品、血浆/血清样品(例如,以能够提取无细胞的DNA)和组织样品。Method 100 may additionally or alternatively include block S150, which may include processing one or more biological samples from a user (e.g., biological samples from different collection sites of a user, etc.). Block S150 may function to facilitate the generation of a microbial dataset for a subject, such as for use in deriving input for a characterization process (e.g., for use in generating microbial-related characterizations for a user, such as by applying one or more microbiome characterization modules, etc.). Thus, block S150 may include receiving, processing, and/or analyzing one or more biological samples from one or more users (e.g., multiple biological samples for the same user over time, different biological samples for different users, etc.). In block S150, the biological sample is preferably generated from the subject and/or the subject's environment in a non-invasive manner. In variations, the non-invasive manner of sample reception may use any one or more of the following: a permeable substrate (e.g., a swab, toilet paper, sponge, etc. configured to wipe a body area of a subject), an impermeable substrate (e.g., a slide, tape, etc.), a container configured to receive a sample from a body area of a subject (e.g., a medicine bottle, a test tube, a bag, etc.), and any other suitable sample receiving element. In a particular embodiment, a biological sample may be collected from one or more of the nose, skin, genitals, mouth, and intestine of a subject in a non-invasive manner (e.g., using a swab and a medicine bottle). However, the biological sample may additionally or alternatively be received in a semi-invasive manner or in an invasive manner. In variations, the invasive manner of sample reception may use any one or more of the following: a needle, a syringe, a biopsy element, a lancet, and any other suitable instrument for collecting a sample in a semi-invasive or invasive manner. In particular embodiments, the sample may include a blood sample, a plasma/serum sample (e.g., to enable extraction of cell-free DNA), and a tissue sample.
在以上变型和实施例中,生物样品可以在没有另外实体(例如,与受试者相关的护理员、医疗保健专业人员、自动或半自动样品收集装置等)的促进的情况下取自受试者的身体,或者可替代地可以在另外实体的协助下取自受试者的身体。在一实施例中,其中在样品提取过程中生物样品在没有其他实体的促进的情况下取自受试者,样品提供试剂盒可以提供给受试者。在该实施例中,试剂盒可包括用于样品获取的一个或多个拭子、配置为接收拭子以用于储存的一个或多个容器、样品提供和用户账户设置的说明、配置为将样品与受试者关联的元件(例如,条形码标识符、标签等)、和允许来自受试者的样品(例如,通过邮件递送系统)递送到样品处理操作的接收器(receptacle)。在另一实施例中,其中生物样品在另外实体的帮助下从受试者提取,一个或多个样品可以在临床或研究背景中从受试者收集(例如,在临床任命期间)。然而,生物样品可以以任何其他合适的方式从受试者接收。In the above variations and embodiments, biological sample can be taken from the body of the subject without the promotion of other entities (e.g., caregivers, healthcare professionals, automatic or semi-automatic sample collection devices, etc.) or can be taken from the body of the subject with the assistance of other entities. In one embodiment, wherein the biological sample is taken from the subject without the promotion of other entities during the sample extraction process, the sample provides a test kit that can be provided to the subject. In this embodiment, the test kit may include one or more swabs for sample acquisition, one or more containers configured to receive the swab for storage, sample provision and user account settings, elements configured to associate the sample with the subject (e.g., barcode identifiers, labels, etc.) and allow the sample from the subject (e.g., by a mail delivery system) to be delivered to the receiver (receptacle) of the sample processing operation. In another embodiment, wherein the biological sample is extracted from the subject with the help of other entities, one or more samples can be collected from the subject in a clinical or research setting (e.g., during a clinical appointment). However, the biological sample can be received from the subject in any other suitable manner.
此外,处理和分析来自受试者的生物样品(例如,用以生成用户微生物数据集等)优选以与上面关于框S110描述的样品接收的实施方案、变型和/或实施例之一、和/或方法100的任何其他合适部分相似的方式执行。这样,可以针对受试者,使用与用于接收和处理生物样品的过程相类似的过程执行框S150中生物样品的接收和处理,那些用于接收和处理生物样品的过程用于生成方法100的表征过程和/或疗法模型,以便提供过程的一致性。然而,框S150中的生物样品接收和处理可以可替代地以任何其他合适的方式执行。In addition, processing and analyzing a biological sample from a subject (e.g., to generate a user microbial data set, etc.) is preferably performed in a manner similar to one of the embodiments, variations, and/or examples of sample reception described above with respect to block S110, and/or any other suitable portion of method 100. Thus, the receiving and processing of the biological sample in block S150 can be performed for the subject using a process similar to the process used to receive and process the biological sample, which is used to generate the characterization process and/or therapy model of method 100, so as to provide consistency of process. However, the receiving and processing of the biological sample in block S150 may alternatively be performed in any other suitable manner.
4.6确定微生物有关特征4.6 Determination of relevant characteristics of microorganisms
方法100可以附加地或可替代地包括框S160,框S160可以包括:诸如基于处理衍生自用户的生物样品的一个或多个微生物数据集(例如,用户微生物序列数据集、微生物组组成数据集、微生物组功能多样性数据集;为提取微生物组特征的微生物数据集的处理;等),利用表征过程针对用户确定微生物有关表征。框S160可以起到针对用户表征一种或多种微生物有关状况的作用,诸如通过从受试者的微生物组衍生数据提取特征、并将特征用作以上在框S130中描述的表征过程的实施方案、变型或实施例中的输入(例如,将用户微生物组特征值用作微生物组有关状况表征模型中的输入,等)。在一实施例中,框S160可以包括基于用户微生物组特征和微生物有关状况表征模型针对用户生成微生物有关表征(例如,在框S130中生成的)。微生物有关表征可以针对任何数量和/或其组合的微生物有关状况(例如,微生物有关状况的组合、单一微生物有关状况和/或其他合适的微生物有关状况等)。微生物有关表征可包括以下一项或多项:诊断(例如,微生物有关状况的存在与否;等);风险(例如,微生物有关状况的发展和/或存在的风险分值;关于微生物有关表征的信息(例如,症状、体征、触发因素、相关联状况等);比较(例如,与其他亚组、群体、用户、诸如历史微生物组组成和/或功能多样性的用户历史健康状态的比较;与微生物有关状况相关联的比较;等),和/或任何其他合适的数据。Method 100 may additionally or alternatively include block S160, which may include: determining microbe-related characterizations for a user using a characterization process, such as based on processing one or more microbe data sets derived from a biological sample of the user (e.g., a user microbe sequence data set, a microbe group composition data set, a microbe group functional diversity data set; processing of a microbe data set to extract microbe group features; etc.). Block S160 may function to characterize one or more microbe-related conditions for a user, such as by extracting features from the subject's microbe group-derived data and using the features as inputs in the embodiments, variations, or embodiments of the characterization process described above in block S130 (e.g., using user microbe group feature values as inputs in a microbe group-related condition characterization model, etc.). In an embodiment, block S160 may include generating microbe-related characterizations for a user (e.g., generated in block S130) based on the user's microbe group features and the microbe-related condition characterization model. The microbe-related characterizations may be for any number and/or combination of microbe-related conditions (e.g., a combination of microbe-related conditions, a single microbe-related condition, and/or other suitable microbe-related conditions, etc.). The microbe-related representations may include one or more of the following: diagnosis (e.g., the presence or absence of a microbe-related condition; etc.); risk (e.g., a risk score for the development and/or existence of a microbe-related condition; information about the microbe-related representation (e.g., symptoms, signs, triggers, associated conditions, etc.); comparison (e.g., comparison with other subgroups, populations, users, historical health states of users such as historical microbiome composition and/or functional diversity; comparisons associated with microbe-related conditions; etc.), and/or any other suitable data.
在另一变型中,微生物有关表征可以包括与微生物组多样性分值相关联(例如,与其相关;与其负相关;与其正相关;等)的微生物组多样性分值(例如,关于微生物组组成、功能等),该微生物组多样性分值与一种或多种微生物有关状况相关。在实施例中,微生物有关表征可以包括随时间推移的微生物组多样性分值(例如,针对随时间推移收集的用户的多个生物样品计算的)、与其他用户的微生物组多样性分值的比较、和/或任何其他合适类型的微生物组多样性分值(例如,确定微生物组多样性分值;使用微生物组多样性分值以确定和/或提供疗法;等)可以以任何合适的方式执行。In another variation, the microbe-related characterization may include a microbiome diversity score (e.g., regarding microbiome composition, function, etc.) associated with (e.g., correlated with; negatively correlated with; positively correlated with; etc.) a microbiome diversity score that is associated with one or more microbiome-related conditions. In an embodiment, the microbiome-related characterization may include a microbiome diversity score over time (e.g., calculated for a plurality of biological samples of a user collected over time), a comparison with a microbiome diversity score of other users, and/or any other suitable type of microbiome diversity score (e.g., determining a microbiome diversity score; using a microbiome diversity score to determine and/or provide a therapy; etc.) may be performed in any suitable manner.
框S160中的确定微生物有关表征优选包括识别与受试者的微生物组组成和/或功能特征相关联的特征和/或特征的组合、将特征输入表征过程、以及接收将受试者表征为属于以下一项或多项的输出:行为组、性别组、饮食组、疾病状态组以及能够通过表征过程识别的任何其他合适组。框S160可以附加地或可替代地包括与受试者的表征相关联的置信指标的生成和/或输出。例如,置信指标可以衍生自:用于生成表征的特征的数量、用于生成表征的特征的相对权重或排名、表征过程中的偏差测量和/或与表征过程的方面相关联的任何其他合适的参数。然而,利用用户微生物组特征可以以任何合适的方式来执行,以生成任何合适的微生物有关表征。Determining microbe-related characterizations in box S160 preferably includes identifying features and/or combinations of features associated with the subject's microbiome composition and/or functional characteristics, inputting the features into a characterization process, and receiving outputs that characterize the subject as belonging to one or more of the following: behavioral groups, gender groups, dietary groups, disease state groups, and any other suitable groups that can be identified by the characterization process. Box S160 may additionally or alternatively include the generation and/or output of a confidence indicator associated with the subject's characterization. For example, the confidence indicator may be derived from: the number of features used to generate the characterization, the relative weight or ranking of the features used to generate the characterization, a deviation measurement in the characterization process, and/or any other suitable parameter associated with an aspect of the characterization process. However, utilizing user microbiome features may be performed in any suitable manner to generate any suitable microbe-related characterization.
在一些变型中,可以用补充特征对从受试者的微生物数据集提取的特征进行补充(例如,从针对用户收集的补充数据中提取的;诸如调查衍生特征、病史衍生特征、传感器数据等),其中这些数据、用户微生物组数据和/或其他合适的数据可用于进一步完善框S130、框S160和/或方法100的其他合适部分的表征过程。In some embodiments, features extracted from a subject's microbiome dataset may be supplemented with supplemental features (e.g., extracted from supplemental data collected for a user; such as survey-derived features, medical history-derived features, sensor data, etc.), where these data, user microbiome data, and/or other suitable data may be used to further refine the characterization process of box S130, box S160, and/or other suitable portions of method 100.
确定微生物有关表征优选地包括诸如通过采用框S130中描述的方法、和/或通过采用本文中描述的任何合适的方法,提取和应用针对用户(例如,基于用户微生物数据集)的微生物组特征(例如,用户微生物组组成多样性特征;用户微生物组功能多样性特征;等)、表征模型、和/或其他合适组件。Determining microbiome-related characterizations preferably includes extracting and applying microbiome features (e.g., user microbiome composition diversity features; user microbiome functional diversity features; etc.) for a user (e.g., based on a user microbiome dataset), characterization models, and/or other suitable components, such as by employing the method described in box S130, and/or by employing any suitable method described herein.
在变型中,如图6所示,框S160可以包括例如在Web界面、移动应用程序和/或任何其他合适的界面处呈现微生物有关表征(例如,从表征中提取的信息等),但是信息的呈现可以以任何合适的方式执行。然而,受试者的微生物数据集可以附加地或可替代地以任何其他合适的方式使用,以增强方法100的模型,并且框S160可以以任何合适的方式执行。In a variation, as shown in FIG6 , block S160 may include, for example, presenting microbial-related representations (e.g., information extracted from the representations, etc.) at a web interface, a mobile application, and/or any other suitable interface, but the presentation of the information may be performed in any suitable manner. However, the subject's microbial dataset may additionally or alternatively be used in any other suitable manner to enhance the model of method 100, and block S160 may be performed in any suitable manner.
4.7促进治疗干预4.7 Facilitating therapeutic interventions
如图9所示,方法100可以附加地或可替代地包括框S170,框S170可以包括(例如,基于微生物有关表征和/或疗法模型)促进针对一个或多个用户的一种或多种微生物有关状况的治疗干预(例如,推广疗法、提供疗法、促进疗法的提供等)。框S170可以起到针对用户推荐、推广、提供和/或以其他方式促进关于一种或多种疗法的治疗干预的作用,例如使用户的微生物组组成和/或功能多样性朝着关于期望的一种或多种微生物有关状况的平衡状态转变(和/或以其他方式改进微生物有关状况的状态等)。框S170可以包括根据受试者的微生物组组成和功能特征向其提供定制疗法,其中定制疗法可以包括微生物配方,该微生物制剂配置为校正具有所识别表征的受试者的生态失调特性。这样,基于训练的疗法模型,框S140的输出可用于直接向受试者推广定制的疗法配方和方案(例如,剂量、使用说明)。附加地或可替代地,疗法提供可以包括推荐可用治疗措施,该可用治疗措施配置为使微生物组组成和/或功能特征朝着期望状态转变。在变型中,疗法可包括以下任何一项或多项:消耗品、局部疗法(例如,洗剂、膏剂、防腐剂等)、药物(例如,与任何合适的药物类型和/或剂量相关联的药物等)、噬菌体、环境治疗、行为改变(例如,饮食改变疗法、压力减轻疗法、身体活动有关疗法等)、诊断程序、其他医学有关程序和/或与微生物有关状况相关联的任何其他合适的疗法。消耗品可包括以下任何一种或多种:食品和/或饮品(例如,益生菌和/或益生元食品和/或饮品类等)、营养补充剂(例如,维生素、矿物质、纤维、脂肪酸、氨基酸、益生元、益生菌等)、消耗性药物和/或任何其他合适的治疗措施。As shown in FIG. 9 , method 100 may additionally or alternatively include block S170, which may include promoting therapeutic interventions for one or more microbial-related conditions for one or more users (e.g., promoting therapy, providing therapy, promoting the provision of therapy, etc.) (e.g., based on the microbial-related representations and/or therapy models). Block S170 may function to recommend, promote, provide, and/or otherwise promote therapeutic interventions for one or more therapies for the user, such as shifting the user's microbiome composition and/or functional diversity toward a desired equilibrium state for one or more microbial-related conditions (and/or otherwise improving the state of the microbial-related conditions, etc.). Block S170 may include providing a customized therapy to a subject based on the subject's microbiome composition and functional characteristics, wherein the customized therapy may include a microbial formulation configured to correct the dysbiosis characteristics of the subject having the identified representations. Thus, based on the trained therapy model, the output of block S140 may be used to promote customized therapy formulations and regimens (e.g., dosages, instructions for use) directly to the subject. Additionally or alternatively, therapy provision may include recommending available therapeutic measures that are configured to transform the microbiome composition and/or functional characteristics toward a desired state. In variations, therapy may include any one or more of the following: consumables, topical therapies (e.g., lotions, ointments, preservatives, etc.), drugs (e.g., drugs associated with any suitable drug type and/or dosage, etc.), bacteriophages, environmental treatments, behavioral changes (e.g., dietary change therapy, stress reduction therapy, physical activity-related therapy, etc.), diagnostic procedures, other medical-related procedures, and/or any other suitable therapy associated with a microbial-related condition. Consumables may include any one or more of the following: food and/or beverages (e.g., probiotics and/or prebiotic foods and/or beverages, etc.), nutritional supplements (e.g., vitamins, minerals, fibers, fatty acids, amino acids, prebiotics, probiotics, etc.), consumable drugs, and/or any other suitable therapeutic measures.
例如,根据疗法模型的输出,商业可获得的益生菌补充剂的组合可以包括针对受试者的适合的益生菌疗法。在另一实施例中,方法100可以包括基于微生物有关状况模型(例如,和/或用户微生物组特征)针对微生物有关状况确定针对用户的微生物有关状况的风险;以及基于微生物有关状况的风险向用户推广疗法。For example, based on the output of the therapy model, a combination of commercially available probiotic supplements may include a suitable probiotic therapy for the subject. In another embodiment, method 100 may include determining a risk of a microbe-related condition for a user for the microbe-related condition based on the microbe-related condition model (e.g., and/or a user microbiome signature); and promoting a therapy to the user based on the risk of the microbe-related condition.
在一变型中,推广疗法可以包括推广诊断程序(例如,用于促进诸如人类行为状况和/或疾病有关状况的微生物有关状况的检测,其可刺激其他疗法的后续推广,诸如用于调节用户微生物组以改进与一种或多种微生物有关状况相关联的用户健康状态;等)。诊断程序可以包括以下任何一项或多项:病史分析、影像学检查、细胞培养测试、抗体测试、皮肤点刺测试、斑贴测试、血液测试、挑战测试、执行方法100的部分、和/或用于促进微生物有关状况的检测(例如,观察、预测等)的任何其他合适程序。附加地或可替代地,诊断设备有关信息和/或其他合适的诊断信息可以处理为补充数据集的一部分(例如,关于框S120,其中这样的数据可以在确定和/或应用表征模型、疗法模型、和/或其他合适的模型中使用;等),和/或关于方法100的任何合适部分收集、使用和/或以其他方式处理(例如,针对用户施用诊断程序以监测关于框S180的疗法功效等)。In one variation, promoting a therapy may include promoting a diagnostic procedure (e.g., for promoting detection of microbial-related conditions such as human behavior conditions and/or disease-related conditions, which may stimulate subsequent promotion of other therapies, such as for regulating a user's microbiome to improve a user's health state associated with one or more microbial-related conditions; etc.). The diagnostic procedure may include any one or more of the following: medical history analysis, imaging examination, cell culture test, antibody test, skin prick test, patch test, blood test, challenge test, performing a portion of method 100, and/or any other suitable procedure for promoting detection (e.g., observation, prediction, etc.) of a microbial-related condition. Additionally or alternatively, diagnostic device-related information and/or other suitable diagnostic information may be processed as part of a supplemental data set (e.g., with respect to block S120, where such data may be used in determining and/or applying a characterization model, a therapy model, and/or other suitable model; etc.), and/or collected, used, and/or otherwise processed with respect to any suitable portion of method 100 (e.g., administering a diagnostic procedure to a user to monitor therapy efficacy with respect to block S180, etc.).
在另一变型中,框S170可以包括推广基于细菌噬菌体(bacteriophage-based)的疗法。更详细地,特异于受试者中代表的某些细菌(或其他微生物)特异的细菌噬菌体的一个或多个群体(例如,以菌落形成单位表示),可用于下调或以其他方式消除某些细菌的群体。这样,基于细菌噬菌体的疗法可用于减少受试者中代表的细菌的不期望群体的大小。作为补充,基于细菌噬菌体的疗法可用于增加未被所用细菌噬菌体靶向的细菌群体的相对丰度。In another variation, frame S170 can include promoting bacteriophage-based therapy. In more detail, one or more populations (e.g., expressed in colony forming units) of bacteriophages specific to certain bacteria (or other microorganisms) represented in the subject can be used to downregulate or otherwise eliminate certain bacterial populations. In this way, bacteriophage-based therapy can be used to reduce the size of undesirable populations of bacteria represented in the subject. In addition, bacteriophage-based therapy can be used to increase the relative abundance of bacterial populations that are not targeted by the bacteriophages used.
在另一变型中,框S170中的疗法提供可以包括向受试者提供关于推荐的疗法、其他形式的疗法、微生物有关表征和/或其他合适的数据的通知。在特定实施例中,向用户提供疗法可以包括:诸如通过在Web界面上显示通知(例如,通过与用户相关联并识别用户的用户帐户;等),(例如,与针对用户提供衍生自微生物有关表征的信息基本同时地,等)提供疗法推荐和/或其他合适的疗法有关信息(例如,疗效;与其他个人用户、用户亚组、和/或用户群体的比较;疗法比较;历史疗法和/或相关联疗法有关信息;诸如用于认知行为疗法的心理疗法指南;等)。可以通过执行应用程序、web界面和/或配置为通知提供的消息客户端的电子设备(例如,个人计算机,移动设备,平板电脑,可穿戴式、头戴式可穿戴计算设备,腕式可穿戴式计算设备等)向受试者提供通知。在一实施例中,与受试者相关联的个人计算机或便携式计算机的网络界面可以通过受试者提供对该受试者的用户帐户的访问,其中用户帐户包括关于用户的微生物有关状况、用户微生物组方面的具体表征(例如,关于与微生物有关状况的相关性;等)的信息,和/或关于(例如,在框S140和/或S170中生成的)建议的治疗措施的通知。在另一实施例中,在个人电子设备(例如,智能电话、智能手表、头戴式智能设备)中执行的应用程序可以配置为(例如,在显示器、触觉上(haptically)、以听觉方式等)提供关于由框S170的疗法模型生成的疗法建议的通知。附加地或可替代地,可以直接通过与受试者相关联的实体(例如,看护人、配偶、重要的其他人、医疗保健专业人员等)提供通知和/或益生菌疗法。在一些其他变型中,通知可以附加地或可替代地提供给与受试者相关联的实体(例如,医疗保健专业人员等),诸如其中该实体能够促进疗法的提供(例如,借助于处方、借助于通过使用计算设备的光学和/或声音传感器的数字远程医疗会议来指导治疗会议,等)。然而,推广通知和/或其他合适的疗法可以以任何合适的方式执行。In another variation, the therapy provision in block S170 may include providing notifications to the subject about recommended therapies, other forms of therapy, microbe-related representations, and/or other suitable data. In a particular embodiment, providing therapy to a user may include: providing therapy recommendations and/or other suitable therapy-related information (e.g., efficacy; comparisons with other individual users, user subgroups, and/or user groups; therapy comparisons; historical therapy and/or associated therapy-related information; such as psychotherapy guidelines for cognitive behavioral therapy; etc.), such as by displaying a notification on a web interface (e.g., by associating with a user and identifying a user's user account; etc.), (e.g., substantially simultaneously with providing information derived from microbe-related representations to the user, etc.). Notifications may be provided to a subject by an electronic device (e.g., a personal computer, a mobile device, a tablet, a wearable, head-mounted wearable computing device, a wrist-mounted wearable computing device, etc.) that executes an application, a web interface, and/or a message client configured to provide notifications. In one embodiment, a web interface of a personal computer or portable computer associated with a subject can provide access to a user account of the subject through the subject, wherein the user account includes information about the user's microbial-related condition, specific characterizations of aspects of the user's microbiome (e.g., about correlations with microbial-related conditions; etc.), and/or notifications about recommended therapeutic actions (e.g., generated in blocks S140 and/or S170). In another embodiment, an application executed in a personal electronic device (e.g., a smart phone, a smart watch, a head-mounted smart device) can be configured to provide notifications (e.g., on a display, haptically, audibly, etc.) about therapeutic recommendations generated by the therapy model of block S170. Additionally or alternatively, notifications and/or probiotic therapies can be provided directly through an entity associated with the subject (e.g., a caregiver, a spouse, a significant other, a healthcare professional, etc.). In some other variations, the notification may additionally or alternatively be provided to an entity associated with the subject (e.g., a healthcare professional, etc.), such as where the entity is able to facilitate the provision of therapy (e.g., by way of prescription, by way of guiding the therapy session via a digital telemedicine session using the computing device's optical and/or acoustic sensors, etc.). However, promoting the notification and/or other appropriate therapy may be performed in any suitable manner.
4.8监测疗法效果4.8 Monitoring the efficacy of therapy
如图7所示,该方法可以附加地或可替代地包括框S180,其列举了:基于处理生物样品,监测疗法对受试者的有效性,以针对用户评估在与益生菌疗法相关联的时间点集合处的微生物组组成和/或功能特征。框S180可以起到聚集附加数据的作用,该附加数据作用关于由给定表征的受试者疗法模型所建议的益生菌疗法的正作用、负作用和/或有效性缺乏。因此,在通过疗法模型(例如,通过在整个治疗中接收和分析来自受试者的生物样品,通过在整个治疗中接收来自受试者的调查衍生数据)推广的治疗进程期间,受试者的监测可以用于针对由框S130的表征过程提供的各表征、以及框S140和S170中提供的各推荐治疗措施,生成疗法有效性模型。As shown in Figure 7, the method may additionally or alternatively include a frame S180, which lists: based on processing biological samples, monitoring the effectiveness of the therapy to the subject, to evaluate the composition and/or functional characteristics of the microbiome at the time point set associated with the probiotic therapy for the user. Frame S180 can play a role in aggregating additional data, which is about the positive effects, negative effects and/or lack of effectiveness of the probiotic therapy suggested by the subject therapy model of the given characterization. Therefore, during the treatment process promoted by the therapy model (e.g., by receiving and analyzing biological samples from the subject throughout the treatment, by receiving survey-derived data from the subject throughout the treatment), the monitoring of the subject can be used for each characterization provided by the characterization process of frame S130, and each recommended treatment provided in frame S140 and S170, Generate a therapy effectiveness model.
在框S180中,可以提示受试者在合并了疗法的治疗方案的一个或多个关键时间点时提供附加的生物样品,并且可以(例如,以与关于框S120描述的方式相似的方式)处理和分析该附加的生物样品以生成表征受试者的微生物组组成和/或功能特征的调节的指标。例如,与以下一项或多项有关的指标和/或任何合适的指标可以用于评估来自微生物组组成和/或功能特征的变化的疗法有效性:早期时间点时受试者微生物组中代表的一个或多个分类组的相对丰度变化,代表受试者的微生物组的特定分类组的变化,受试者微生物组的第一分类组细菌的丰度和第二分类组细菌的丰度之间的比例,受试者微生物组中的一种或多种功能家族的相对丰度变化。附加地或可替代地,来自受试者的、属于受试者在治疗时的经历(例如,经历的副作用、改进的个人评估、行为改变、症状改进等)的调查衍生数据可以用于确定框S180中疗法的有效性。例如,方法100可以包括:接收来自用户的治疗后生物样品;收集来自用户的补充数据集,其中补充数据集描述用户对疗法(例如,确定的和推广的疗法)的依从性和/或其他合适的用户特征(例如,行为、状况等);基于微生物有关状况表征模型和治疗后生物样品,生成关于微生物有关状况的第一用户的治疗后微生物有关表征;以及基于治疗后微生物有关表征(例如,基于治疗后微生物有关表征与治疗前微生物有关表征之间的比较;等)和/或用户对疗法的依从性(例如,基于用户微生物组关于微生物有关状况的积极或消极结果改变疗法;等),针对微生物有关状况向用户推广更新疗法。附加地或可替代地,其他合适的数据(例如,描述与人类行为状况相关的用户行为的补充数据;描述诸如观察到的症状的疾病有关状况的补充数据;等)可以在确定治疗后表征(例如,关于微生物有关状况的治疗前到治疗后的变化程度等)、更新的疗法(例如,基于有效性和/或对所推广的疗法的依从性确定更新的疗法等)中使用。疗法有效性、附加生物样品的处理(例如,用以确定附加的微生物有关表征、疗法等)和/或与关于微生物有关状况的连续的生物样品收集、处理和分析相关联的其他合适方面,可以以任何合适的时间和频率执行,以生成、更新和/或以其他方式处理模型(例如,表征模型、疗法模型等)、和/或用于任何其他合适的目的(例如,作为与方法100的其他部分相关联的输入)。然而,框S180可以以任何合适的方式执行。In block S180, the subject may be prompted to provide additional biological samples at one or more key time points of the treatment regimen incorporating the therapy, and the additional biological samples may be processed and analyzed (e.g., in a manner similar to that described with respect to block S120) to generate indicators characterizing the modulation of the composition and/or functional characteristics of the subject's microbiome. For example, indicators related to one or more of the following and/or any suitable indicators may be used to assess the effectiveness of the therapy from changes in the composition and/or functional characteristics of the microbiome: changes in the relative abundance of one or more taxonomic groups represented in the subject's microbiome at early time points, changes in a specific taxonomic group representing the subject's microbiome, the ratio between the abundance of bacteria in the first taxonomic group and the abundance of bacteria in the second taxonomic group of the subject's microbiome, changes in the relative abundance of one or more functional families in the subject's microbiome. Additionally or alternatively, survey-derived data from the subject's experience with the subject during treatment (e.g., side effects experienced, improved personal assessments, behavioral changes, symptom improvements, etc.) may be used to determine the effectiveness of the therapy in block S180. For example, method 100 may include: receiving a post-treatment biological sample from a user; collecting a supplemental data set from the user, wherein the supplemental data set describes the user's compliance with a therapy (e.g., a determined and promoted therapy) and/or other suitable user characteristics (e.g., behavior, condition, etc.); generating a post-treatment microbe-related characterization of a first user for a microbe-related condition based on a microbe-related condition characterization model and the post-treatment biological sample; and promoting an updated therapy for the microbe-related condition to the user based on the post-treatment microbe-related characterization (e.g., based on a comparison between the post-treatment microbe-related characterization and the pre-treatment microbe-related characterization; etc.) and/or the user's compliance with the therapy (e.g., changing the therapy based on a positive or negative result of the user's microbiome for the microbe-related condition; etc.). Additionally or alternatively, other suitable data (e.g., supplemental data describing user behavior related to human behavior conditions; supplemental data describing disease-related conditions such as observed symptoms; etc.) may be used in determining a post-treatment characterization (e.g., the extent of change from pre-treatment to post-treatment for the microbe-related condition, etc.), an updated therapy (e.g., determining an updated therapy based on effectiveness and/or compliance with the promoted therapy, etc.). Therapy effectiveness, processing of additional biological samples (e.g., to determine additional microbe-related characterizations, therapies, etc.), and/or other suitable aspects associated with continuous biological sample collection, processing, and analysis of microbe-related conditions can be performed at any suitable time and frequency to generate, update, and/or otherwise process models (e.g., characterization models, therapy models, etc.), and/or for any other suitable purpose (e.g., as input associated with other portions of method 100). However, block S180 can be performed in any suitable manner.
然而,方法100可以包括任何其他合适的框或步骤,其被配置为促进来自受试者的生物样品的接收、来自受试者的生物样品的处理、分析衍生自生物样品的数据以及生成模型,该模型可用于根据受试者的特定微生物组组成和/或功能特征提供定制诊断和/或基于益生菌的疗法。However, method 100 may include any other suitable blocks or steps configured to facilitate receiving a biological sample from a subject, processing the biological sample from the subject, analyzing data derived from the biological sample, and generating a model that can be used to provide customized diagnostics and/or probiotic-based therapies based on the subject's specific microbiome composition and/or functional characteristics.
系统和/或方法的实施方案可以包括各种系统组件和各种方法过程的每种组合和置换(permutation),各种系统组件和各种方法过程包括任何变型、实施例和特定实施例,其中本文中描述的方法和/或过程可以通过和/或使用本文中描述的系统、元件和/或实体的一个或多个实例,异步(例如,依序)、同时(例如,平行)、或以任何其他合适的顺序执行。Embodiments of the systems and/or methods may include every combination and permutation of the various system components and the various method processes, including any variations, embodiments, and specific embodiments, wherein the methods and/or processes described herein may be performed asynchronously (e.g., sequentially), simultaneously (e.g., in parallel), or in any other suitable order by and/or using one or more instances of the systems, elements, and/or entities described herein.
本文中描述的变型中的任何一种(例如,实施方案、变型、实施例、特定实施例、图示等)和/或本文中描述的变型的任何部分可以附加地或可替代地组合、排除和/或以其他方式应用。Any of the variations described herein (e.g., embodiments, variations, examples, specific examples, illustrations, etc.) and/or any portion of the variations described herein may be additionally or alternatively combined, excluded, and/or applied in other ways.
该系统和方法及其实施方案可以至少部分地体现和/或实施为配置成接收存储计算机可读指令的计算机可读介质的机器。指令优选地通过计算机可执行组件来执行,该计算机可执行组件优选与系统整合。计算机可读介质可以存储在任何合适的计算机可读介质上,例如RAM、ROM、闪存、电可擦除只读存储器(EEPROM)、光学设备(CD或DVD)、硬盘驱动器、软盘驱动器或任何合适的设备。该计算机可执行组件优选是通用或专用处理器,但是任何合适的专用硬件或硬件/固件组合设备可以可替代地或附加地执行指令。The system and method and embodiments thereof may be at least partially embodied and/or implemented as a machine configured to receive a computer-readable medium storing computer-readable instructions. The instructions are preferably executed by a computer-executable component, which is preferably integrated with the system. The computer-readable medium may be stored on any suitable computer-readable medium, such as RAM, ROM, flash memory, electrically erasable read-only memory (EEPROM), optical devices (CD or DVD), hard drives, floppy disk drives, or any suitable device. The computer-executable component is preferably a general-purpose or special-purpose processor, but any suitable special-purpose hardware or hardware/firmware combination device may alternatively or additionally execute the instructions.
如本领域技术人员将从先前的详细描述以及从附图和权利要求书中认识到的,可以在不脱离所附权利要求中限定的范围的情况下对实施方案进行修改和改变。As those skilled in the art will recognize from the previous detailed description and from the accompanying drawings and claims, modifications and changes may be made to the embodiments without departing from the scope defined in the appended claims.
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Claims (15)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762545039P | 2017-08-14 | 2017-08-14 | |
| US62/545,039 | 2017-08-14 | ||
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